Individualizing Hormone Therapy to Minimize Risk

Accurate Assessment of Risks and Benefits

Donna Shoupe


Women's Health. 2011;7(4):475-485. 

In This Article

Factors that Affect the Risk–Benefit Profile of Hormone Therapy

When evaluating the WHI or any study in regards to the risk–benefit profile for hormone therapy, there are important factors (Box 4) that should be considered as they have a profound effect on the risks and benefits.

The timing hypothesis simply says that timing of initiation is critical to understanding the therapeutic actions of estrogen. This theory is supported by large numbers and varieties of studies that consistently demonstrate an optimum therapeutic window for initiation of estrogen therapy.[15–17] The risks are increased if hormone therapy is started after 60 years or after more than 10 years since menopause (Figure 1 & Table 1).[18,25,26] Many studies, including trials on bone loss, urogenital atrophy, dementia and cardiovascular diseases, also demonstrate that the optimum benefit profile is achieved by initiation of estrogen therapy during this window.

Figure 1.

Overall risk and benefit are profoundly affected by age of initiation of therapy.
CHD: Coronary heart disease; VTE: Venous thromboembolism; WHI: Women's Health Initiative.
Data taken from.[18,25,26]

Another important factor to consider in an overall risk–benefit assessment is the dose of estrogen. There is substantial evidence that while low-dose estrogen is effective for menopausal symptoms[27] and for the prevention of bone loss[28] and other specific diseases associated with the low menopausal levels of estrogen, lower doses are associated with fewer side effects[27] and lowered risks.

Use of transdermal estrogen therapy adds a specific additional safety benefit as it avoids the hepatic 'first pass' effect thus avoiding changes in clotting factors and sex hormone-binding globulin. Multiple studies show no increased risk of blood clots and venous thromboembolism, even in high-risk postmenopausal women when transdermal estrogen is used.[29,30]


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.