Hormone replacement therapy (HRT) refers to the hormones that are generally taken by women at menopause to relieve symptoms associated with menopause, such as hot flashes and vaginal dryness. HRT was also believed to prevent osteoporosis and reduce risk of cardiovascular disease. However, these beliefs are no longer supported by medical literature.
HRT has been shown to increase breast cancer risk. However, the magnitude of this increase in breast cancer risk varies greatly across studies. The relative risk of using HRT ranges from 1.2 to 1.9. The evidence seems to indicate that a combination of estrogen and progesterone, often referred to as combined HRT (CHRT), is responsible for increasing breast cancer risk.
Combined HRT Increases Estradiol Level
A high level of estradiol has been associated with higher risk of breast cancer. The relative risk per doubling of free estradiol level is 1.50, with a 95 percent confidence interval between 1.22 and 1.85.
Combined hormone replacement therapy (CHRT) has been shown to raise a woman's levels of estradiol and sex hormone binding globulin (SHBG).
Addition of Progestin Increases the Risk of Breast Cancer
The increased risk of breast cancer due to HRT based only on estrogen is negligible. HRT only increases the risk of breast cancer when adding progestin. A typical dose of CHRT consists of 0.625mg per day of conjugated equine estrone and 2.5mg per day of progestin. This is also the dose given in the Women's Health Initiative randomized controlled trial. It still remains uncertain whether different classes of progestins have different effects on breast cancer risk.
Different Modes of Delivery Might Have Different Effects on Risk
Furthermore, it has been shown that an increase in breast cancer risk is associated with exposure of breast tissue to hormone. Thus, different forms of delivery might lead to different levels of increased risk. In the transdermal form of hormone delivery, the patient is only exposed to low doses of hormones with first pass clearance by the liver. On the other hand, in the oral form of hormone delivery, the patient experiences an initial peak in hormone level, followed by clearance from the blood. This suggests that trans-dermal delivery of CHRT might have a lower risk of breast cancer than oral delivery.
Complex Interactions Between BMI and HRT
In postmenopausal women who do not use HRT, the risk of breast cancer increases with increasing BMI. That is, obese women have a higher risk of breast cancer than normal-weight women. However, for post-menopausal women who do use HRT, there is no increased risk of breast cancer due to higher BMI, and in fact some studies show a slight decrease in risk with high BMI.
References
- Key, T. e. (2002). Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. Journal of the National Cancer Institute , 606-616.
- Nachtigall, L. e. (2000). Serum estradiol-binding profiles in postmenopausal women undergoing three common estogen replacement therapies: associations with sex hormone-binding globulin, estradiol, and estrone levels. Menopause , 7 (4), 243-250.
- Opatrny et al., Hormone replacement therapy use and variations in the risk of breast cancer, An International Journal of Obstetrics & Gynaecology ISSN: 1471-0528 (Online) ISSN: 1470-0328 (Print) Volume 115, Issue 2, 2008. Pages: 169--175
