Hormones & Cancer

In this article, our goal is to delve into the research of hormones and to educate healthcare providers on various mechanisms of how estrogen induces apoptosis (cell suicide), for example, as an anti-cancer effect.

Estrogen receptors are located in numerous organs of the human body, including breast, bladder, bones, arteries, vagina, heart, liver, uterus, mitochondria, and brain. Women may begin to exhibit decline in hormone levels during peri-menopause which can start as early as age 35 . Thus, some women may have 15 years before menopause (defined as a lack of menses for 12 months). Proper education and treatment from healthcare providers can alleviate the progression of symptoms, increase quality of life, and potentially lower tumor-causing mortality.

Deficiency of estrogen and progesterone results in an inflammatory state, negatively affecting the cardiovascular system, neurocognitive function, and musculoskeletal integrity¹. Moreover, low menopause estrogen levels are known to be a key player in the development and progression of some (45%) breast cancer^2,3.

The WHI study concluded that women taking Premarin and Provera resulted in increased rate of breast cancer⁴. However, Premarin and Provera are not bioidentical to the chemical structure that the human body naturally produces.

In 2005, Fournier studied 54,000 women taking bioidentical estrogen and progesterone and found that this group of women had a 10% decrease in risk of breast cancer. In comparison, he found that the group of women taking estrogen with synthetic progestin had 40% increase risk of breast cancer. In a follow up study after 8 years, Fournier discovered that the rate of breast cancer risk increased to 69% in the progestin group . It also appears that the progestin may be the reason for the increase in breast cancer findings, NOT the estrogen. These findings suggest that bioidentical hormone replacement therapy is advantageous over synthetic estrogen and progestin, and appears to be safer.

In breast glands, estradiol has been proposed to both stimulate cell proliferation and also inhibit cell apoptosis in several different pathways. Studies show that in hormone-dependent breast cancer cells, estradiol can undergo an adaptation in which it transforms from a growth promoting agent to inducing apoptosis. This is exhibited in long term deprivation of estrogen in breast tissues. Haddow et. al reported that women with breast tumors who have been in menopause for greater than 10 years had better response to estrogen therapy compared to women who were in menopause for 5 years or less⁶. Researchers proposed that long term deprivation of estrogen increases the sensitization of estrogen to apoptotic effects. In addition, Ellis and colleagues also concluded that estrogen therapy can halt tumor progression by 25% in women with metastatic breast cancer and who are resistant to standard non-hormonal therapy⁷.

Regulating cell apoptosis is crucial in the event of DNA damage, defective cell cycle, and other severe cell stress⁴. The two main cell survival signaling pathways and their checkpoints in apoptosis make up the complex balance that is critical to the integrity of healthy systems. The first signaling pathway, AKT or protein kinase B (PKB), is considered a target for cancer therapies. Estradiol has been shown to inhibit the P13K/AKT signaling pathway thereby inducing apoptosis of cancer cells. Estradiol also has been shown to decrease cell proliferation by significantly reducing AKT phosphorylation².

The second main signaling pathway is the nuclear factor NF-kB pathway. Estradiol has been shown to inhibit NF-kB activity which results in activation of p53-dependent apoptosis². Research by Osipo et al. concluded that in tamoxifen-resistant tumors, estradiol treatment remarkably down regulated NF-kB activity, thereby producing anti-proliferation and pro-apoptotic effects⁸. These proposed mechanisms may explain the many clinical outcomes which point to bioidentical estrogen and progesterone in lowered rate of cancer-related mortality and decreased rate of reoccurrence of breast cancer.

Read more on Studies are Showing Bioidentical Hormones are Safe here

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