Aromatase: Part One

Aromatase: Part One

In the last newsletter (Women at Greater Risk for Eye Diseases), we discovered that low estrogen played a part in the development of eye diseases in women, and yet simply giving women estrogen replacement therapy (ERT) came with certain dangers, including increased risk of breast cancer. This newsletter focuses on aromatase, and how blocking this chemical in the body can protect women, and men, from health issues related to hormonal imbalances.

Hormone-dependent cancers

Breast and prostate cancer are the most common noncutaneous (“not related to the skin”) cancers in women and men, worldwide.  Breast cancer is the second leading cause of cancer-related deaths among women in North America, however survival rates for breast cancer are quite high (91% survival at 5 years after diagnosis, and 80% at 15 years).

Among males, prostate cancer is also the most commonly diagnosed noncutaneous malignancy, and also the second leading cause of cancer death among men, worldwide. But the survival rate is also good, with 99% 5-year survival rates in North America.  Currently, both of these gender-specific cancers are treated with endocrine therapy and hormones.

(“The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs.” – Source)

Breast Cancer

The high rates of breast cancer survival are attributed to endocrine therapy targeting hormone receptors in hormone receptor–positive breast cancer (which constitute 83% of invasive breast cancers).  Similarly, prostate cancer is considered hormone-related, and “is treated with androgen deprivation therapy and other systemic therapies, including chemotherapy and medical or surgical induction of castrate levels of testosterone”.

To summarize, breast cancer is related to too much estrogen, and prostate cancer is related to too much androgens (male sex hormones, of which testosterone is the primary one).  The primary medical treatment for breast cancer is to use  tamoxifen, or a class of drugs known as aromatase inhibitors (e.g. anastrozole).

“Tamoxifen blocks estrogen from connecting to the cancer cells and telling them to grow and divide. While tamoxifen acts like an anti-estrogen in breast cells, it acts like an estrogen in other tissues, like the uterus and the bones. Because of this, it is called a selective estrogen receptor modulator (SERM)”. (Source)

Whereas, aromatase inhibitors cause a systemic reduction in estradiol (the primary form of estrogen produced by the body) by “counteracting the estradiol-mediated negative hypothalamic-pituitary feedback system”. Thus, aromatase inhibitors lower total estrogen without raising levels elsewhere in the body (as the tamoxifen does), suggesting a safer form of treatment.

Studies have found that tamoxifen has either no impact on heart disease risk, or leads to a “reduction in cardiovascular events with an increase in venous thromboembolic events via its estrogen-agonistic effects. In contrast, aromatase inhibitors are associated with higher cardiovascular risks than tamoxifen, but whether this reflects aromatase inhibitor–related toxicity or a protective effect of tamoxifen remains uncertain”.   (Source)

This is a rather long detour into the science of anti-aromatase drugs in order to get to the point that, while they may be a safer alternative for treating breast cancer, given they are drugs they still come with some dangers (including “a modest increase in bone resorption”, which is a precursor to osteoporosis).

Aromatase

The enzyme aromatase is found in those estrogen producing cells located in the adrenal glands, brain, ovaries, placenta, testicles, and in some fat tissue. High levels of aromatase results in converting excessive amounts of testosterone and progesterone into estrogen. And too much estrogen can be dangerous, for both women and men.  Estrogen dominance, and high aromatase activity, are associated with breast, uterine and ovarian cancers in women, and breast, colon, and prostate cancers in men. In women, other symptoms include fibrocystic breast disease, cervical dysplasia, endometriosis, infertility, PMS, and uterine fibroids.    (Source)

In men, other symptoms of excess aromatase, and estrogen dominance, include anxiety and depression, belly fat, breast enlargement, fatigue, urinary tract issues, and reduced libido and muscle mass.

Men and Estrogen

Men do have a need for some estrogen, just as women have a need for some testosterone, however research over the last 15 years has indicated that in men estrogen is responsible for a number of effects originally attributed to testosterone.  For example, in men “estradiol has an important role in gaining and maintaining bone mass, closing of the epiphyses and the feedback on gonadotropin secretion”.

(“Epiphysis is the rounded end of a long bone, its primary function is to connect adjacent bones to form joints.”

“The gonadotropins are peptide hormones that regulate ovarian and testicular function and are essential for normal growth, sexual development and reproduction.” )

So, aromatase (a form of enzyme) is responsible for converting androgens to estrogens. And, while too little estrogen in men can lead to symptoms of low bone density, unfused epiphyses, and excessively high testosterone levels (at extreme, linked to violent criminal behavior), an excess of estrogen is also associated with negative symptoms (“premature closure of the epiphyses, gynecomastia and low gonadotropin and testosterone levels”).

Therefore, some therapies are now based on lowering estrogen levels in men, especially for treating “disorders including pubertas praecox (puberty occurring at an unusually early age), the andropause (our version of menopause) and gynecomastia (a condition of overdevelopment or enlargement of the breast tissue in men or boys)”.  (Source)

Just like we give women synthetic estrogen for treating menopause, and then have to worry about increasing breast cancer risk, so the medical profession will give men synthetic testosterone to treat andropause, but then must monitor the prostate to watch for increased cancer risk.

However, if doctors use aromatase inhibitors instead of HRT, the male’s testosterone levels rise safely, and the prostate is protected. By using anti-aromatase substances testosterone is forbidden from breaking down into estrogen and thus the male has more free testosterone available for his day to day hormone needs (sexuality, muscle mass, vigor ,and vitality).   (Source)

Reduction of testosterone is the current treatment protocol for prostate cancer, however recent research is suggesting that “estrogens may play a role together with androgens in the genesis of benign prostatic hyperplasia (BPH) in man”. And scientists are proposing that “aromatase inhibitors may find application in non-surgical treatment of BPH”.  (Source)

In animals and humans, estrogens stimulate prostate growth, and studies seem to indicate that estrogen metabolites contribute to prostate cancer: “In the prostatic tissue, estradiol appears to cause DNA changes and make it lose its regulatory control”.  (Source)

So, BPH (enlargement of the prostate) can be caused by estrogens (as well as metabolites of testosterone), and BPH can increase PSA (prostate-specific antigen) levels, which are in turn linked to increased risk of prostate cancer.  (Source)

Therefore, if we reduce BPH, via aromatase inhibitors, it must follow that we also reduce our risk of prostate cancer.

Moreover, “aromatase inhibitors may be an attractive alternative for traditional testosterone substitution in elderly men because these compounds can be administered orally once daily and may result in physiological 24 h testosterone profiles. Additionally, misuse of aromatase inhibitors is unlikely since testosterone levels will not be stimulated to vastly supraphysiological levels”.   (Source)  Which means that anti-aromatase compounds could also be a safe way to treat andropause, muscular wasting, and erectile dysfunction (all related to low testosterone).

Where is all this heading?

We have established the value of aromatase inhibitors, for both men and women, but have also found that there may be some risks and side effects associated with these drugs. However, guess what? There are many natural anti-aromatase substances, the subject of which is the primary objective of this long-winded roundabout. So long winded that we’ve run out of time, so tune in next week for Aromatase–Part Two: Natural Aromatase Inhibitors