What are the risks of Hormone Replacement Therapy (HRT)?

From the Guidelines

Hormone Replacement Therapy (HRT) is associated with significant risks, including an increased chance of blood clots, stroke, and heart disease, and should be used with caution and under close medical supervision. The risks of HRT are well-documented in the literature, with a study published in the Annals of Internal Medicine in 2002 1 concluding that the harms of estrogen-progestin therapy are likely to outweigh the chronic disease prevention benefits for most women. This study found that 10,000 women taking estrogen and progestin for 1 year might experience 7 additional coronary heart disease (CHD) events, 8 more strokes, 8 more pulmonary emboli, and 8 more invasive breast cancers.

Some of the key risks associated with HRT include:

• Increased risk of blood clots, stroke, and heart disease, particularly in older individuals or those with existing cardiovascular conditions
• Slightly higher risk of breast cancer, with risk increasing the longer HRT is used
• Potential risks of gallbladder disease, increased risk of endometrial cancer if estrogen is taken without progestin by women with an intact uterus, and a possible increased risk of ovarian cancer with long-term use
• Side effects such as breast tenderness, bloating, headaches, mood changes, and vaginal bleeding

The specific risk profile varies based on the type of HRT (estrogen-only or combined), dosage, duration of use, age at initiation, and individual health factors. Lower doses used for shorter periods typically carry fewer risks. Patients with a history of certain cancers, liver disease, unexplained vaginal bleeding, history of blood clots, or stroke should generally avoid HRT. Regular monitoring by a healthcare provider is essential to assess ongoing benefits versus risks for each individual, as recommended by the USPSTF 1.

From the FDA Drug Label

The WHI estrogen plus progestin substudy reported a statistically significant 2-fold greater rate of VTE was reported in women receiving daily CE(0.625 mg) plus MPA (2. 5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus. The most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the WHI substudy of daily CE (0.625 mg)-alone. The WHI estrogen plus progestin substudy reported an increased risk of invasive breast cancer in women who took daily CE plus MPA. The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer. In the WHIMS estrogen-alone ancillary study of WHI, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg)-alone or placebo.

The risks of Hormone Replacement Therapy (HRT) include:

• Venous Thromboembolism (VTE): a 2-fold increased risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) 2
• Endometrial Cancer: an increased risk of endometrial cancer, especially with unopposed estrogen therapy, with a risk 2-12 times greater than non-users 2
• Breast Cancer: an increased risk of invasive breast cancer, especially with estrogen plus progestin therapy, with a relative risk of 1.24 and an absolute risk of 41 versus 33 cases per 10,000 women-years 2
• Ovarian Cancer: a statistically non-significant increased risk of ovarian cancer, with a relative risk of 1.58 and an absolute risk of 4 versus 3 cases per 10,000 women-years 2
• Probable Dementia: an increased risk of probable dementia, with a relative risk of 1.49 and an absolute risk of 37 versus 25 cases per 10,000 women-years 2

From the Research

Risks of Hormone Replacement Therapy (HRT)

The risks associated with HRT are numerous and can be categorized into several areas, including:

• Breast cancer: Studies have shown that HRT may increase the risk of breast cancer, particularly for formulations that contain both estrogen and progesterone 3, 4, 5, 6.
• Cardiovascular health: HRT has been linked to an increased risk of stroke and venous thromboembolism (VTE), although there is also evidence of a possible cardioprotective effect 3, 5.
• Endometrial cancer: The use of HRT containing estrogen alone has been shown to increase the risk of endometrial cancer, while the addition of progestagen may counteract this effect 4.
• Thrombosis and emboli: HRT has been associated with an increased risk of thrombosis and emboli 7.
• Other risks: HRT may also increase the risk of other health problems, such as osteoporosis and Alzheimer's disease 7.

Factors that Influence the Risks of HRT

Several factors can influence the risks associated with HRT, including:

• Type of HRT: The type of HRT used, such as estrogen-only or combined estrogen and progesterone, can affect the risk of breast cancer and other health problems 4, 6.
• Duration of use: The length of time HRT is used can also impact the risk of breast cancer and other health problems 3, 6.
• Individual risk factors: A woman's individual risk factors, such as a family history of breast cancer or a history of cardiovascular disease, can also influence the risks associated with HRT 7, 5.
• Body mass index (BMI): A woman's BMI can also affect the risks associated with HRT, with leaner women being at higher risk of breast cancer 6.