How Hormones Interact with Receptor Sites

How Hormones Interact with Receptor Sites (and the Relation to Breast and Prostate Cancers)

Written by Carol Petersen, RPh, CNP – Women’s International Pharmacy

There is no shortage of information and opinions concerning hormone treatments or the “best” way to test for hormone deficiencies, not to mention how to use hormones or confirm if a hormone intervention is working. However, upon reading Dr. Edward Friedman’s book, The New Testosterone Treatment: How You and Your Doctor Can Fight Breast Cancer, Prostate Cancer, and Alzheimer’s, it occurred to me that hormone receptors are really THE thing we should examine. Regardless of the testing method, the specific hormone, or its intended result, all hormone action occurs at the receptor sites.

What are Receptors?

Receptors are protein structures designed to snag passing hormones. Receptors for hormones that poke through the cell membrane are called membrane receptors. Other receptors are inside the cell (intracellular receptors) in the cytosol, and more receptors are in the cell nucleus. The number of receptors is not stagnant, and varies according to nutrients and the environment.

Once a receptor captures a hormone, that cell receives instructions for an action, such as cell replication, manufacturing other proteins, moderating cell activity, and programming abnormal cell death. A single hormone can produce action within minutes of binding. Receptors manipulate the cell’s action by upregulating or down-regulating the production of proteins.

Hormones Have Affinities

Conventional practitioners insist that as long as a hormone receptor receives a hormone–whether it is identical to the human hormone or not–all hormones and hormone-like substances should be considered equal. This thinking completely ignores the research identifying different affinities for different hormone receptors. As an example, the hormone estriol is generally considered a weak estrogen. This is because the binding of estriol on a receptor, in comparison to estradiol binding on the same receptor, produces less response.

In sharp contrast, the receptors for estrogen in the urinary tract, bladder, and vaginal tissue have a much greater affinity for estriol. A study published in the New England Journal of Medicine demonstrated dramatic differences in effectiveness in treating urinary tracts in elderly women with recurrent infection. Clinically, estriol also shines when treating vaginal dryness, outperforming estradiol and other estrogens.

Receptors are Promiscuous

Even though receptors have affinities, they are not very discriminating about binding and can be affected by synthetic hormones as well as “the real thing.” Receptor activity can be blocked or accentuated. For example, medroxyprogesterone acetate, a progestin rather than real progesterone, not only interferes with progesterone receptors but can block testosterone and cortisol receptors too. Because testosterone has such a positive effect on potential breast and prostate cancer (see below), this could help explain why this synthetic hormone is so frequently associated with increases in breast cancer, as reported in the Women’s Health Initiative study.

A Hormone Receptor Model

Dr. Friedman, a theoretical biologist, describes the hormone “big picture” and also offers a theory on what he calls the Hormone Receptor Model. He believes that his model answers questions about how breast and prostate cancer initiate, and how this information can be used to target very specific treatment based on bioidentical hormones (particularly testosterone) to change the course of these diseases. Dr. Friedman states that breast and prostate cancer are fundamentally identical in their causes, presentation, and progression.

Introducing Bcl-2

Bcl-2 is a protein produced by hormone stimulation in the cell nucleus of cancer cells. This protein is of high importance in the discussion of breast and prostate cancer. Cancer cells are immortal; they escape the normal program for cell death called apoptosis. The Bcl-2 protein shields cancer cells from their normal cell destruction.

Estrogen Receptors

Estrogen Receptor Beta (ER-Beta) stimulation has a positive result, which is that the production of the Bcl-2 protein is down-regulated, thus depriving cancer cells of their immortality. Moreover, it also has an anti-inflammatory effect.

Estrogen Receptor Alpha (ER-Alpha) increases inflammation and the production of the Bcl-2 protein. When breast cancer tissue is examined and reported as estrogen receptor positive, that information is incomplete. We need to know the concentrations of the different estrogen receptors. A dominance of ERBeta receptors is good. One feature of cancer cells is that the further the cancer progresses, the more ERAlpha receptors are available.

Types of Estrogen and Their Binding Properties

Estradiol binds to both alpha and beta receptors with equal strength. Estrone binds to alpha receptors five times more tightly than to beta receptors, and estriol binds to ER-beta 3.2 times more tightly than it will bind to ER-alpha. So, the amount of Bcl-2 being produced is dependent upon which estrogen is binding, how strongly it is binding, and the concentration of each type of receptor. Hence, estrone is considered to be potentially more pro-cancer, while estriol is considered to be potentially more anti-cancer.

Progesterone Receptors

Progesterone Receptor B diminishes the production of Bcl-2 when activated, thereby also depriving cancer cells of their immortality. Fortunately, Receptor Bs tend to predominate, making the presence of progesterone typically more anti-cancer than pro-cancer.

Progesterone Receptor A increases Bcl-2 and stimulation of this type of receptor is associated with BRCA1 and BRCA2 mutations. According to Dr. Friedman, the few women with these mutations also have increased numbers of Progesterone Receptor A. In turn, this leads to an increased Bcl-2 production protecting cancer cells. He outlines a different strategy to use in this situation (please refer to Dr. Friedman’s book for more detailed information).

Androgen Receptors

The membrane androgen receptor behaves differently in men than it does in women. In women, stimulation of this receptor causes a decrease in Bcl-2; in men, it causes an increase in Bcl-2. In both men and women, stimulation of the intracellular androgen receptors decrease Bcl-2 and also causes the production of other anti-cancer proteins. However, if there is a shortage of testosterone to stimulate the intracellular receptors, the shortage favors more cancer cell growth.

Dr. Friedman’s Synopsis

The above summary is a very simplistic synopsis of Dr. Friedman’s views on hormone receptors and their role in diseases. A synopsis of Dr. Friedman’s treatment program includes the following:

  • He suggests that Vitamin D (which is a hormone) should always be considered first and foremost with a diagnosis of breast or prostate cancer. There is no downside to ensuring that vitamin D levels are optimized, and activation of the vitamin D receptor helps destroy cancer cells. (Please see our newsletter Vitamin D: The Sunshine Hormone for more information.)
  • He states that ample amounts of testosterone are very protective against both breast and prostate cancer.
  • He advises on the use of aromatase inhibitors to hamper the conversion of testosterone to estrogens, which can lead to more activation of ER-alpha receptors.
  • He believes that estriol is underutilized, and that it could be supplemented generously to shift stimulation to the ER-Beta receptors. Premarin®, with its predominance of estrone, clearly is a therapy that shifts the stimulation to the ER-Alpha receptors.

Dr. Friedman offers some very thought-provoking ideas about using bioidentical hormones in the treatment of breast and prostate cancer. Although his theory is not yet tested, some practitioners have already begun incorporating elements of it.

A study recently published by Dr. Rebecca Glaser illustrates strong evidence for the idea that testosterone can be protective, and perhaps even effective as a treatment for breast cancer. She recently presented the results of 1,268 women who were receiving testosterone treatment along with an aromatase inhibitor. Although her study is designed for ten years, she is already observing a dramatic decrease in breast cancer incidence in her study group, as compared to other studies and population statistics, at the five-year mark.

Dr. Friedman feels that his methods are not intended to be a “cure” but a means to control cancer. He claims that the only side-effect is that, instead of suffering from the disfigurement and secondary effects of cancer surgery, radiation, and the debilitation of hormone deprivation and chemotherapy drugs, restoring hormones to more youthful levels will yield a zest for life while living with cancer.

How Hormones Interact with Receptor Sites2018-05-21T15:01:18-05:00

Can Testosterone Protect Against Breast Cancer?

Can Testosterone Protect Against Breast Cancer?

Written by Kathy Lynch, PharmD – Women’s International Pharmacy


Compounded testosterone therapy for women has been prescribed for years in this country. Since testosterone can convert to estrogen in the body, practitioners are sometimes hesitant to prescribe it, thinking that testosterone might increase a woman’s chance of getting breast cancer.

Dr. Rebecca Glaser and her colleague Constantine Dimitrakakis set out to examine this assumption. They designed the Testosterone Implant Breast Cancer Prevention Study to explore the relationship between testosterone subcutaneous implants and breast cancer. This study looked at 1,268 pre- and postmenopausal women who received either testosterone or testosterone-anastrozole (an estrogen blocker) implants. These same women were not using systemic estrogen therapy.

While the time period for this study is ten years, an analysis conducted at the five-year mark reported a breast cancer rate that was less than 50% of the rate reported in previous menopausal hormone replacement therapy studies. Study participants who most closely adhered to the testosterone regimen experienced an even lower rate of breast cancer. According to the National Cancer Institute’s surveillance program, more than twice as many cases of breast cancer would be expected in this particular study population if no specific interventions were made.

Dr. Glaser believes that these interim study results support her theory that testosterone use does not increase the occurrence of breast cancer. Further studies are warranted. Different dosage forms, as well as the possibility that testosterone therapy might protect against breast cancer, should be studied.

Can Testosterone Protect Against Breast Cancer?2018-04-03T17:20:42-05:00

Bioidentical Progesterone vs. Synthetic Progestins

Bioidentical Progesterone vs. Synthetic Progestins

Written by Kathy Lynch, PharmD – Women’s International Pharmacy

There is nothing that bothers bioidentical hormone proponents more than to have the scientific community categorize bioidentical progesterone with synthetic progestins. In 2002, the Women’s Health Initiative (WHI) study found a slight increase in breast cancer risk for women using conjugated equine estrogens (CEE) with medroxyprogesterone acetate (MPA). In spite of the fact that the study authors cautioned that their results did not necessarily apply to bioidentical progesterone, the popular press has put progesterone in the same category with MPA ever since.

More recent studies support the fact that, contrary to popular belief, MPA and progesterone do not have the same breast cancer risk. Two of these studies occurred in France, where bioidentical hormones are widely used. A study published in 2008 found that, of the 2,354 cases of invasive breast cancer found among 80,377 postmenopausal women, estrogen plus progesterone hormone therapy did not increase the risk of invasive breast cancer while estrogen plus synthetic progestins did. A later study published in 2013 supported these findings.

Progesterone may indeed be beneficial in protecting women against breast cancer. A breast cancer cell-line study supports the theory that progesterone actually causes the destruction of specific breast cancer cells. Another study found that progesterone reduced estradiol-induced growth of female breast tissue when applied 10-13 days before breast surgery. Still another study found that women with progesterone blood levels = or > 4ng/ml before breast cancer surgery had the best survival rate.

It is time that we stop espousing quasi-science by equating bioidentical progesterone with synthetic progestins. They are not the same and never will be.

  • Rossouw JE, et al. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled Trial. JAMA. 2002 Jul 17;288(3):321-33.
  • Fournier A, et al. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.Breast Cancer Res Treat. 2008 Jan; 107(1): 103-111. Epub 2007 Feb 27.
  • Cordina-Duverger E, et al. Risk of Breast Cancer by Type of Menopausal Hormone Therapy: a Case-Control Study among Post-Menopausal Women in France. PLoS One. 2013 Nov; 8(11):e78016. doi: 10.1371/journal.pone.0078016. eCollection 2013.
  • Formby B, Wiley TS. Progesterone Inhibits Growth and Induces Apoptosis in Breast Cancer Cells: Inverse Effects on Bcl-2 and p53. Ann Clin Lab Sci. 1998; 28(6):360-369.
  • Chang KJ, et al. Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril. 1995 Apr; 63(4):785-793.
  • Mohr PE, et al. Serum progesterone and prognosis in operable breast cancer. Brit J Cancer. 1996 Jan 16; 73:1552-5.
Bioidentical Progesterone vs. Synthetic Progestins2018-04-03T11:05:28-05:00

Ingrid Edstrom’s Proactive Breast Wellness Program

Ingrid Edstrom’s Proactive Breast Wellness Program

Written by Carol Petersen, RPh, CNP – Women’s International Pharmacy


Our current medical system has been designed to take our hands and give us direction when disease has become evident, but it has left us sadly wanting when it comes to prevention. Finding and accessing the information necessary to prevent disease is difficult and time consuming. And, even if we do find it, interpreting it and understanding it may take some help.

Thankfully, a comprehensive compilation of what we currently know about keeping our breasts free from disease, including breast cancer, is available as an engaging multimedia presentation offered by Ingrid Edstrom, FNP, MEd, CTT. The Proactive Breast Wellness Program is her magnus opus and a labor of love.

A nationally certified family nurse practitioner, Edstrom combined her nursing degree with a minor in clinical nutrition. She also earned a master’s degree in Health Education, and has completed clinical training programs at the Mind Body Medical Institute. Ingrid Edstrom has skillfully combined all of her educational and clinical skills, and gift wrapped them in a delightful presentation so that we would have the resources we need to keep our breasts healthy.

Edstrom includes information about the various effects that hormones have on the breasts, the type of diet and foods that can be used to improve breast health, and the environmental issues affecting the breast. She even includes a meditation so that listeners can help reduce high cortisol, making us aware of the emotional and spiritual aspects of dealing with our breasts and our bodies.

The Power of Progesterone

Edstrom’s presentation covers a complete program for breast health, but let’s just focus in on one section she calls “The Power of Progesterone” as a sample. She states that after age 35, many women cease having ovulatory cycles, even though they continue to bleed regularly. This lack of ovulation increases the estrogenic dominance by 100 times. Add on the burden of many environmental exposures to estrogen-like compounds (which she also covers extensively) and the normal counter balance of progesterone for estrogen is greatly diminished.

Quoting Dr. John Lee, Edstrom maintains that progesterone should be used for breast cancer protection, during breast cancer treatment, and after breast cancer treatment. She also cites Dr. Susan Love, a breast surgeon, who recommends that any breast surgery should be done on days 13 through 28 of the menstrual cycle (progesterone levels are higher then) or, if that is not possible, progesterone cream should be applied to the breasts for two weeks before the planned surgery. Published studies have documented better outcomes when progesterone plays a role.

Edstrom discusses the problems with artificial progestins and brings up the issue of California’s mandatory cancer warning labeling on the over-the-counter progesterone products. She points out that California rule makers depended upon compilations of studies that primarily involved progestins, and then concluded erroneously that the required warning should pertain to progesterone as well. Progesterone, itself, has not been proven to be a carcinogen but instead offers protection. She cites the studies that demonstrate this.

Edstrom also discusses various dosage forms at length and details her preferences. She gives practical hints on how to use different dosage forms and offers some clinical suggestions. For example, she recommends that progesterone creams not be applied to the abdomen because this application may have the most significant effect in slowing gut motility. She learned from compounding pharmacists that progesterone cream applied directly to dense or thickened areas of the breasts may have the best results. She likes to use progesterone drops prepared with organic jojoba oil, and warns that progesterone is in suspension in this dosage form and should therefore be shaken very thoroughly before using to ensure proper dispersion.

Screening Methods

A cornerstone of Edstrom’s presentation, as well as her clinical practice, is the use of breast thermography as a tool for early warnings of issues presenting in the breast. Thermography is not an invasive test but captures the subtle differences in the temperature of the skin in a color scale. As might be imagined, the hot spots indeed appear as yellow to red colors, while normal temperatures appear in the blue and green ranges. The temperatures and color differences show areas of increased metabolic activity in the breast tissue long before a mass that could be palpated would form or would appear on a mammogram. This imaging allows for early interventions and also allows for a measure of the success of the interventions.

While mammograms are firmly entrenched in our medical system, there are some negative aspects with this type of testing. Mammograms introduce radiation (a known carcinogen) into our bodies. Mammograms do not prevent breast cancer and are not the best tool for an early warning. Both false negatives and false positives are common. Mammograms can actually damage or spread cancerous cells because of the high pressure applied to breasts in order to obtain the imaging. Breasts that are lumpy or have thick tissue present problems for accurate diagnoses with mammograms.

Thermography, on the other hand, measures physiologic changes rather than physical. As a cancer tumor develops, new blood vessels are formed feeding the tumor. This enhanced metabolic activity is easily detected with thermograms. Additionally, the increased metabolic activity can show up three to eight years before a tumor has actually developed. A suspicious thermogram can be followed up with an MRI, and neither of these diagnostic techniques subjects the body to radiation.

Edstrom thinks that thermography may replace mammography as the primary early screening tool in the not too distant future. She says that other screening methods are also being developed, such as a way to test fluid expressed from the nipples for cancer cells, and a saliva assay to test for a protein linked to breast cancer.

A Proactive Approach

As the incidence of breast cancer has steadily risen, we probably all know someone who has been affected. Ingrid Edstrom’s Proactive Breast Wellness Program is information that every one of us can use and benefit from, whether we are worried about breast cancer, are undergoing breast cancer treatment, or need to know how to prevent a reoccurrence.

If Ingrid Edstrom can be successful in her proactive approach to breast health, then the pink ribbon campaigns will become history. Just imagine the progress that would be made if women gathered in their neighborhoods, or their book clubs and coffee shops, and listened to presentations like this together, with the chance to discuss and disseminate the valuable information she offers. Let’s change the campaign from “breast cancer awareness” to “breast health awareness.” We encourage you to take advantage of Ingrid’s gift to us!

We were pleasantly surprised to see that Edstrom references several of our Connections newsletters when she covered the topic of hormones and balance. She also links to a collection of abstracts on hormone therapies that we compiled and published. Please feel free to explore these resources for additional information that may contribute to your breast health awareness.

Ingrid Edstrom’s Proactive Breast Wellness Program2018-04-02T16:49:13-05:00

Promoting Breast Health

Promoting Breast Health: The Facts about Breast Cancer Detection and Prevention

Written by Carol Petersen, RPh, CNP – Women’s International Pharmacy

A diagnosis of breast cancer certainly strikes terror in the hearts of women. The latest statistics suggest that 1 out of every 8 women in the United States will develop breast cancer. The cancer experts claim that your best defense against breast cancer is early detection so that it can be treated. Unfortunately, this philosophy makes your odds of getting breast cancer seem like a game of roulette, where you have no recourse when your number is up. But that’s simply not true. Let’s review the facts.

One of the most basic methods of early detection – and actually the most accurate (as high as 90%) – is regular breast self-exams. A confounding factor for self-exams (as well as other detection methods) is the presence of various lumps in the breast. Most of the time, these lumps will be deemed harmless and not necessarily precancerous. However, these easily dismissed lumps could be a signal that something is not quite right. For example, breast lumps have been linked to hormonal and nutritional imbalances. In a personal study of one, I can attest that when I started to use progesterone at about the age of 45, most of the lumps in my breasts disappeared.  I had been getting yearly mammograms and suffered with premenstrual tender breasts for about 20 years prior.  Dr. Eugene Shippen recommended the addition of iodine for me and the last, largest lump disappeared. He calls this lumpy affliction “cauliflower breasts.”

The presence of any lumps in the breasts, or cyclical breast tenderness or pain, should be explored. A self-exam is the starting point. A breast self-exam can be enhanced by using breast exam pads, which are actually FDA-approved devices consisting of two plastic sheets that sandwich liquid between them. When you use these pads during a breast self-exam, your fingers are able to detect even more subtle changes in the texture of your breast tissue. If you think you feel something unusual in your breast, trust your gut and get it checked by your healthcare practitioner.

At present, the standard method for breast cancer detection continues to be mammography. Industry sources claim that the amount of radiation is small. However, the effects of radiation are cumulative, and some individuals may be exposed as many as four times per breast in one session. Premenopausal breasts are very sensitive to radiation, and radiation exposure has been identified as a cancer initiator and promoter.

Another potential issue with mammography is that the trauma inflicted on the breast while being compressed between the two plates could have serious consequences if breast cancer exists. The encapsulated cancer cells in the breast could be dislodged and spread into the blood stream.

Mammography is not very effective at early detection because cancer typically exists for eight years or more before it is detectable on a mammogram. Mammography also produces a large number of both false positive (benign breast lumps) and false negative readings. An improved three-dimensional mammography device was announced recently, which may improve the imaging and therefore its effectiveness, but each scan delivers twice as much radiation as a regular mammogram.

Breast thermography first appeared several decades ago, but it has been slow to catch on because mammography is so entrenched in the medical industry. With thermography, the equipment measures very small changes in temperature and produces an image (thermogram) of the breast tissue. Precancerous and cancerous tissues are more active metabolically (i.e., “hotter”), which makes them identifiable on a thermogram. This detection method offers significant advantages, including:

  • It can detect metabolic changes in advance of an active cancer.
  • It can detect cancers in the underarm area, a frequent site for breast cancer, which is not detectable by mammography.
  • The breasts are not exposed to radiation.
  • The breasts do not need to be compressed.

Dr. Samuel Epstein claims that a breast self-exam, verified with a breast exam by a trained professional, offers much more accuracy with lower cost and far less trauma for the breasts. Therefore, Dr. Epstein believes this should be the standard detection method rather than mammography or other devices.

In addition to regular self-exams, other measures you can take to help keep your breasts healthy include:

  • Maintain hormone balance. Make sure your body has enough progesterone, and that estrogens are not dominant or accumulating.
  • Get enough iodine, which is essential for healthy breasts, and vitamin D, which is believed to help protect the breasts.
  • Decrease or stop caffeine if your breasts are sensitive.
  • Make sure that the lymph glands around your breasts and under your arms are not constricted by tight fitting bras or clothing. These glands help carry toxins from the breast area.
  • Avoid using antiperspirants containing aluminum, especially right after shaving under the arms. Because the most frequent site of breast cancer is near the underarm area, aluminum is believed to be associated with breast cancer.

With reliable information and a conscious decision to take good care of your body, you are more likely to beat the odds of losing a breast to cancer.

Promoting Breast Health2018-04-09T14:13:36-05:00