Natural Products Targeting Aromatase Gene Promoters
Among the natural products tested as AIs, phytoestrogens, such as flavones and isoflavones are able to bind ER and induce estrogen action . The binding characteristics and the structural requirements necessary for the inhibition of human aromatase by flavones and isoflavones were obtained by using computer modeling and confirmed by site-directed mutagenesis . It was found that these compounds bind to the active site of aromatase in an orientation in which their rings A and C mimic rings D and C of the androgen substrate, respectively . Until now ~ 300 natural products, most of them are phytoestrogens, have been evaluated for their ability to inhibit aromatase using noncellular , cell-based, and in vivo aromatase inhibition assays however, only a few studies have been reported for their effect on aromatase promoter I.4, I.3/II activity . The exact mechanisms how these plant products adapted to inhibit aromatase gene expression or enzyme activity is not fully understood.
Figure 3
What Type Of Breast Cancer Is Treated With Hormones
Adjuvant therapy for early-stage breast cancer: Tamoxifen is FDA approved for adjuvant hormone treatment of premenopausal and postmenopausal women with ER-positive early-stage breast cancer, and the aromatase inhibitors anastrozole, letrozole, and exemestane are approved for this use in postmenopausal women.
Our Natural Estrogen Blocker: Estro Clear
Estro Clear is an all-natural, clinical-grade estrogen blocker for men. Estro Clear works as part of a healthy diet and lifestyle to help reduce excess estrogen for men with estrogen dominance or low testosterone levels.
Studies show the active ingredients in this natural hormone treatment have a clear anti-estrogenic effect. This, therefore, helps to rebalance your hormone levels which have a positive impact on your sexual and prostate health. Moreover, by lowering their estrogen level, men can regain their masculine traits and may find it easier to lose weight naturally.
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What Is The Link Between Estrogen And Breast Cancer
About 8 out of 10 breast cancers are hormone receptor-positive. These cancers need estrogen, progesterone or both hormones to grow. Excess exposure to estrogen raises cancer risk. Excess exposure can occur because of:
- Hormone replacement therapies for menopause.
- Naturally high estrogen levels.
- Klinefelter syndrome, a genetic condition affecting men.
In the past, some men took estrogen to treat prostate cancer. Healthcare providers rarely use this treatment now because it increases the risk of male breast cancer.
Natural Alternatives To Hormone Therapy
Protection against uterine cancer vs. the risk of breast cancer. The decision to take estrogen and progesterone supplements can be daunting. In the world of women’s health, it could be the decision of decisions: Should I take hormone replacement therapy? The considerations can be so deep, and the scientific debates so confusing, many women are turning to herbal and food supplements, hoping they will calm the symptoms of menopause while staving off heart disease and osteoporosis.
Though the science is still young, research offers some encouragement for women seeking non-pharmaceutical ways to cut down on mood swings and hot flashes.
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What Should I Know About Storage And Disposal Of This Medication
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture .
It is important to keep all medication out of sight and reach of children as many containers are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location â one that is up and away and out of their sight and reach.
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDAâs Safe Disposal of Medicines website for more information if you do not have access to a take-back program.
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Inhibitory Agents Of Aromatase Promoter I3/ii
There are several potential synthetic agents available for inactivation of aromatase promoter I.3/II. Studies in human breast adipose fibroblasts revealed that sodium butyrate, peroxisome proliferator activated receptor agonists, retinoid X-receptor agonists, and inhibitors of p38 and JNK are capable of inhibiting aromatase promoter I.3/II activity. The action of these agents has been summarized in a recent review by Chen et al . However, these synthetic products are also known to induce side effects. Troglitazone, rosiglitazone and pioglitazone are PPAR agonists . These drugs caused edema, reduced hemoglobin and hematocrit levels, increased plasma LDL-and HDL cholesterol and increased body weight . The RXR agonist LG101305 induced hypertriglyceridemia, hypercholesterolemia, hypothyroidism and leucopenia. Sodium butyrate induced bradycardia while p38 inhibitor SB202190 is toxic to liver and the JNK inhibitor AS601245 have no reported side effects compared to others .
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Estrogen Dominance And Hormone Imbalance
Remember that estrogen isnt all bad. You need it! But our sex hormones dont exist alone in a bubble. The ratio of estrogen alongside other hormones like progesterone and testosterone can impact how estrogen acts in your body and how much of it you should have during different phases of life.
While estradiol rules your reproductive years, it should naturally drop after menopause. Women with higher estradiol in postmenopausal years appear to have an increased risk of breast cancer. This makes sense as our estrogen levels should naturally drop once we enter menopause.
But, due to lifestyle and environmental factors , women in their 40s and 50s can experience estrogen dominance even after going through menopause.
And while the risk of breast cancer tends to be higher for postmenopausal women, theres some indication that high estrogen levels can increase the risk of breast cancer diagnosis even before menopause. It is challenging to study this for women who still get their periods, though, since estrogen levels fluctuate so much during the month, so the studies arent as reliable.
Evidence From The Historical Use Of Estrogens To Treat Metastatic Breast Cancer
The application of high-dose estrogen therapy for the treatment of metastatic breast cancer was the first use of a chemical therapy to treat any cancer successfully . Estrogen therapy became the standard of care to treat metastatic breast cancer in postmenopausal patients until the introduction of tamoxifen , a nonsteroidal antiestrogen . Tamoxifen became the gold standard for the treatment of ER-positive breast cancer for the next 20 years. Estrogen was all but abandoned as a treatment option, but Ingle and colleagues completed a provocative trial of tamoxifen versus the synthetic estrogen diethylstilbestrol in metastatic breast cancer . Responses were equivalent with fewer side effects with tamoxifen, but a re-analysis years later demonstrated that survival was significantly improved with DES .
Towards the end of his distinguished career, Professor Sir Alexander Haddow FRS reflected on the remarkable responses noted with estrogen in some tumors, often when treatment was more than a decade past menopause: The extraordinary extent of tumour regression observed in perhaps 1% of post-menopausal cases has always been regarded as of major theoretical importance, and it is a matter for some disappointment that so much of the underlying mechanisms continues to elude us.
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If Cancer Has Come Back Or Spread
Hormone therapy can be used to treat breast cancer that has come back or that has spread to another part of the body .
Its given either alone or with other treatments, depending on what treatments you had before.
If your breast cancer came back during or after treatment with hormone therapy, you may be offered a different type of hormone therapy.
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Adjuvant Hormonal Therapy Treatment Time
For many years, women took hormonal therapy for five years after surgery for early-stage, hormone receptor-positive breast cancer. In most cases, the standard of care is five years of tamoxifen, or two to three years of tamoxifen followed by two to three years of an aromatase inhibitor, depending on menopausal status.
Recent research has found that in certain cases, taking tamoxifen for 10 years instead of five years after surgery lowered a womans risk of recurrence and improved survival.
In most cases, a post-menopausal woman diagnosed with early-stage, hormone receptor-positive breast cancer would take an aromatase inhibitor for five years after surgery to reduce the risk of recurrence. After that, if breast cancer had been found in the lymph nodes, called node-positive disease, a woman would take an aromatase inhibitor for an additional five years, for a total of 10 years of hormonal therapy treatment.
Doctors call taking hormonal therapy for 10 years after surgery extended adjuvant hormonal therapy.
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What Is Unique About The Young Mammary Gland That Makes It So Susceptible To Cancer Induction And Protection
The fact that two crucial reproductive events, menarche and young age at parity, have the greatest effect on lifetime breast cancer risk suggests that the young mammary gland represents a crucial window in tumorigenic susceptibility. Why this is the case is less clear. Based on the epidemiological evidence for this, a few hypotheses have been generated, but again few have been tested experimentally, and this work is largely restricted to rodent models.
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Hormones And Postmenopausal Breast Cancer
Despite the negative results of the WHI study, the relationship between hormones, breast cancer, and other health indicators is far from conclusive. Prior to the use of tamoxifen, estrogen therapy was actually the standard for the treatment of breast cancer . Early comparisons of estrogen vs. tamoxifen treatment revealed that the synthetic estrogen DES provided as much protection as tamoxifen treatment . In addition, more recent analyses of the Womens Health Initiative data have shown that in hysterectomized women, estrogen replacement therapy alone actually seemed to decrease the incidence and mortality rate of breast cancer 70075-X/abstract” rel=”nofollow”> Anderson et al., 2012).
Due to the confusion related to hormone therapy and breast cancer, meta-analyses of multiple studies have been conducted. In 2006, such an analysis indicated that hormone replacement therapy taken after breast cancer was related to a decreased risk of breast cancer deaths . Creasman reviewed studies on hormone replacement therapy after cancer, finding that case-control and cohort studies found no risk or even less risk of recurrence of breast cancer in women taking estrogen therapy. He concluded that hormone therapy has little if any risk to women who have had breast cancer.
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When Are Hormone Blockers Used
Hormone inhibitors and blocker options may depend on a persons stage of life.
- Hormone inhibitors are only used in postmenopausal women. They can be given to premenopausal women if steps are taken by the treatment team to put the ovaries to sleep by blocking the ovaries from producing estrogen or progesterone.
- Hormonal therapy may also be called anti-hormone treatment. Think of it as the opposite of hormone replacement therapy . If pathology tests show that the tumor in your breast has hormone receptors , then hormonal therapy may be recommended for you after the completion of your acute treatment .
- Hormonal therapy keeps breast cancer cells from receiving or using the natural female hormones in your body which they need to grow. Hormonal therapy also blocks the ability of health breast cells to receive hormones that could stimulate breast cancer cells to regrow again in the form of recurrence of the breast cancer within the breast or elsewhere in the body.
Is There A Natural Estrogen Blocker
Natural estrogen blockers
Wild nettle root: Nettle root or nettle leaves are often used to make prostate medication. Nettles contain compounds that act as natural estrogen blockers. Taking supplements can regulate production of the hormone. Chrysin: This flavonoid is found in passionflower, honey, and bee propolis.
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What Types Of Hormone Therapy Are Used For Breast Cancer
Several strategies are used to treat hormone-sensitive breast cancer:
Blocking ovarian function: Because the ovaries are the main source of estrogen in premenopausal women, estrogen levels in these women can be reduced by eliminating or suppressing ovarian function. Blocking ovarian function is called ovarian ablation.
Ovarian ablation can be done surgically in an operation to remove the ovaries or by treatment with radiation. This type of ovarian ablation is usually permanent.
Alternatively, ovarian function can be suppressed temporarily by treatment with drugs called gonadotropin-releasing hormone agonists, which are also known as luteinizing hormone-releasing hormone agonists. By mimicking GnRH, these medicines interfere with signals that stimulate the ovaries to produce estrogen.
Estrogen and progesterone production in premenopausal women. Drawing shows that in premenopausal women, estrogen and progesterone production by the ovaries is regulated by luteinizing hormone and luteinizing hormone-releasing hormone . The hypothalamus releases LHRH, which then causes the pituitary gland to make and secrete LH and follicle-stimulating hormone . LH and FSH cause the ovaries to make estrogen and progesterone, which act on the endometrium .
Examples of ovarian suppression drugs are goserelin and leuprolide .
Blocking estrogens effects: Several types of drugs interfere with estrogens ability to stimulate the growth of breast cancer cells:
What Are The Three Hormones That Run The Male And Female Reproductive Systems
In her book Molecules of Emotion, author and scientist Candace Pert shares with us accumulated environmental pollutants within our bodies are mimicking and disrupting the action of our sex hormones estrogen, progesterone, and testosterone which run the male and female reproductive systems..
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How Hormone Therapy Works
Oestrogen and progesterone are hormones which are naturally produced in the human body. Before menopause, oestrogen is mostly produced by the ovaries. After menopause, when the ovaries are no longer active, a small amount continues to be produced in other tissues such as fat, muscle and adrenal glands.
Normal breast cells contain receptors that are able to recognise these hormones and allow them to access the cells, where they release signals encouraging growth and development. All breast cancers are tested for the presence of these oestrogen and progesterone receptors, using tissue taken at the time of biopsy or surgery. Approximately 70% of breast cancers retain these receptors, and rely on these hormones to grow. These hormone-sensitive cancers are described as oestrogen receptor positive and/or progesterone receptor positive .
Hormone therapy is also used to shrink or slow the growth of a breast cancer when surgery is not appropriate, for example in an older person with other major health issues. It is also used to help shrink advanced stage breast cancers or slow their growth.
Hormone therapy for breast cancer is not the same as HRT . HRT raises the level of oestrogen +/- progesterone in the body and is not used in the treatment of breast cancer.
What Are Aromatase Inhibitors
To begin with, I want to be very clear that you should never stop any prescription medications without discussing this with your primary care doctor.
Aromatase inhibitors are hormonal therapies used to treat estrogen-positive breast cancer. Common names for these drugs are Aromasin, Anastrozole, and Letrozole. They are technically designed to stop tumor growth and recurrence. Aromatase inhibitors are typically used to treat postmenopausal women with ER-positive breast cancer. They are not usually given to pre-menopausal women because they dont block the estrogen production in the ovaries.
The main goal of these drugs is to block the synthesis of estrogen from testosterone by the enzyme aromatase. The drugs block the action of this enzyme and thereby lower the estrogen level it may slow the growth of cancers and lower the risk of recurrence.
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Length Of Treatment With An Aromatase Inhibitor
Randomized clinical trials have compared outcomes for women who used aromatase inhibitors for 10 years versus 5 years . Taking an aromatase inhibitor for 10 years :
- Improves disease-free survival
- Lowers the risk of cancer in the opposite breast
However, overall survival is the same whether a woman takes an aromatase inhibitor for 5 years or 10 years . For most women, the benefit of the extra 5 years of treatment is small .
Women who take an aromatase inhibitor for more than 5 years continue to have side effects from the drug, including a higher number of bone fractures and a higher rate of osteoporosis .
Talk with your health care provider about how long you should take an aromatase inhibitor.
Learn about the importance of completing treatment with an aromatase inhibitor.
Possible side effects of aromatase inhibitors include muscle pain, joint pain and menopausal symptoms .
Aromatase inhibitors also cause a loss of bone density. Youll get a baseline measure of your bone density so changes in your bone density can be monitored.
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Natural Estrogen Blockers For Men
Some medications block the enzyme aromatase. They include letrozole, anastrozole, exemestane, and many others. However, women with breast cancer are the ones who typically use them.
By dropping their estrogen levels, they stop the effects of estrogen on cancer cells and slow down cancer growth. In men, they can also balance testosterone and estrogen levels. However, theres a natural way to do it through a natural estrogen blocker.
In this section, we will name and explain the most important estrogen blockers for men:
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