Risks of Bioidentical Progesterone in Hormone Replacement Therapy
Bioidentical progesterone has a more favorable safety profile compared to synthetic progestins, but still carries risks including potential increased risk of cardiovascular events, venous thromboembolism, and breast cancer when used in combination with estrogen.
Cardiovascular and Thrombotic Risks
Bioidentical progesterone has important risk considerations when used in hormone replacement therapy:
- Stroke risk: HRT containing progesterone is associated with increased stroke incidence (8 additional strokes per 10,000 women-years) 1, 2
- Coronary heart disease: Combined estrogen-progesterone therapy showed increased CHD events (7 additional events per 10,000 women-years) 1, 2
- Venous thromboembolism: HRT with progesterone increases VTE risk (RR 2.14), with highest risk in the first year of use 3, 2
However, bioidentical progesterone appears to have a more favorable cardiovascular profile than synthetic progestins:
- Oral micronized progesterone has a better cardiovascular and thrombotic risk profile than synthetic progestins 1
- Natural progesterone does not negatively affect blood lipids or vasculature as many synthetic progestins do 4
- Studies suggest bioidentical hormones may carry reduced risk of blood clots compared to non-bioidentical preparations 4
Cancer Risks
When considering cancer risks:
- Breast cancer: Combined estrogen-progestin therapy is associated with increased breast cancer risk (8 additional cases per 10,000 women-years) 1
- However, a meta-analysis of studies involving 86,881 postmenopausal women reported that natural progesterone was associated with significantly lower breast cancer risk compared to synthetic progestins 5
- Endometrial cancer: Progesterone provides necessary endometrial protection when used with estrogen 1, 2
- Ovarian cancer: The WHI study showed a statistically non-significant increased risk of ovarian cancer with combined HRT (RR 1.58) 2
Other Risks
Additional risks to consider:
- Dementia: Increased risk of probable dementia in women 65-79 years old using combined HRT 2
- Gallbladder disease: Increased risk (RR 1.8-2.5) with HRT use, higher with long-term use 1
- Visual abnormalities: Retinal vascular thrombosis has been reported with estrogen therapy 2
Clinical Considerations for Bioidentical Progesterone Use
When prescribing bioidentical progesterone:
- Oral micronized progesterone is the preferred progestin for HRT due to its more favorable cardiovascular and thrombotic risk profile 1
- The typical dose of oral micronized progesterone is 200 mg daily 1
- Progesterone can be administered in sequential or continuous regimens depending on clinical needs 3
- Absolute contraindications include history of hormone-dependent cancers, venous thromboembolism, active liver disease, unexplained vaginal bleeding, and history of stroke or coronary heart disease 1
Important Caveats
- The USPSTF explicitly recommends against using HRT for chronic disease prevention (Grade D recommendation) 3, 1
- HRT should be used at the lowest effective dose for the shortest possible time for symptom management 3
- Individual risk factors (cardiovascular disease, cancer history, thrombotic risk) should be carefully assessed before initiating therapy 1
- Regular monitoring remains important to assess for potential side effects 1
Despite some favorable evidence for bioidentical progesterone compared to synthetic progestins, the USPSTF concluded that the harmful effects of estrogen and progestin are likely to exceed chronic disease prevention benefits in most women 3.