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 Sites 2018-05-21T15:01:18+00:00

Vaginal Use of Estriol

Vaginal Use of Estriol

Pharmacy Staff – Women’s International Pharmacy

woman with tulipsEstriol is one of the three main estrogens made in a woman’s body. The other estrogens are estrone and estradiol. Estriol levels are highest in a woman’s body during pregnancy. Normal ranges for non-pregnant, non-menopausal and menopausal women are not usually noted, making it difficult to determine what would be considered “normal levels” in the body. Estriol is the weakest estrogen of the three. It may be used alone or in combination with the other estrogens in a number of different dosage forms, and has been shown in studies to have good activity in the vaginal area. In 1993, a landmark study published by Raul Raz et al. in the New England Journal of Medicine sparked great interest in using estriol vaginally, not only for improving the condition of the urinary tract, but vaginal tissue as well.[i]

In 2016, Salvatore Caruso et al. published a study in Menopause reaffirming the effectiveness of vaginally-used estriol.[ii] This study included monitoring the acidity of the vaginal tissue. Healthy vaginal tissue is in the slightly acidic range and favors the growth of friendly lactobacillus acidophilus bacteria. When this tissue becomes thinner and more alkaline as estrogen declines in menopause, the protection of the friendly bacteria declines, which may lead to infections by other less desirable organisms. Even the small amount of estriol used in this study, 50 microgram doses, caused an improvement in cell structure, acidity of the vaginal tissue, better urine control, and increases in sexual function and in quality of life. The study concluded that estriol should be a first choice in managing menopausal symptoms in the genital and urinary tracts in menopausal women.

Also in 2016, Filippo Murina et al. studied the application of a 25 microgram dose of estriol (applied daily with a finger or cotton swab) to the vulvar vestibule. After the study period of 12 weeks over 80% of the participants experienced relief from pain on intercourse. The authors maintain that direct application of estriol to the vestibule, rather than applying it vaginally, is necessary for pain relief.[iii]

Estrogen receptors

Although in reality, the process is much more complex, a simplified description of estrogen’s interaction with its receptors begins with an estrogen hormone binding to an estrogen receptor protein. When bound, the estrogen hormone-estrogen receptor complex is shuttled to the cell nucleus, where it gives specific DNA instructions and produces proteins to create an estrogen effect. This description is complicated by discoveries that there is more than one type of estrogen receptor (alpha and beta). The beta type tends to predominate in the mucosal areas, such as the vagina. The higher affinity of estriol to beta receptors over other estrogens such as estradiol predicts that estriol might be more effective in those tissues. (For more on this topic, see our article, How Hormones Interact With Receptor Sites.)

Labial Adhesions

Estrogens are sometimes used to treat labial adhesions in babies and young girls. Estriol may be the preferred choice because of its strong affinity to mucosal estrogen receptors. A study published in 2016 by Stefanie Bussen et al. demonstrated a favorable outcome in comparison to manual or surgical separation. A 1 milligram estriol dose was applied in this study nightly for four weeks at the fusion site. In most of the cases, further treatment was not needed.[iv]

Commercially Available Abroad

Estriol has been in use both as an oral and a topical estrogen supplement for many years in other countries. A product named Ovestrin, which contains a half milligram of estriol per dose, is government-approved for use in many countries.[v] The recommended dosing of estriol for the genital tract and urinary tract atrophy is one dose nightly for some weeks, then decreasing to a maintenance dose of twice weekly applications as symptoms improve. As the cells normalize and normal bacteria and acidity is re-established, issues such as infection, inflammation, pain on intercourse, dryness, itching, urinary complaints, and mild incontinence may resolve.

Estriol in the United States

Estriol has had a tumultuous time in the United States. Since there was no commercial product available, compounding pharmacists came to the rescue by preparing estriol containing creams or other dosage forms in varying strengths for individual use. The drug company Wyeth (the makers of Premarin and Prempro until purchased by Pfizer in 2009) sought to have the FDA ban its use in the United States, even while selling a commercial product containing estriol in Europe.[vi] To this date, there is no human drug product containing estriol in the United States which has been approved by the FDA. At this time, it is solely available through compounding pharmacies.

Ironically, there is an estriol product for animals approved by the FDA for use in spayed (the surgical removal of the ovaries and uterus) female dogs with estrogen-responsive urinary incontinence. Urinary incontinence is a common problem in spayed female dogs because the removal of the ovaries depletes hormones, including estrogens. This drug, Incurin, contains 1 mg of estriol in tablets.[vii]

Conclusion

The use of estriol vaginally is a clear illustration that our current medical system, based on government approvals and a one-size-fits-all model, leaves large therapy gaps. As of the time of this writing, no drug company in the United States has succeeded in bringing an estriol-containing product to market for human use. In the meantime, compounding pharmacists have made estriol available in a wide array of dosage forms and doses to address each woman’s individual needs.

  • [i] Raz R, et al. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993 Sep 9;329(11):753-6.
  • [ii] Caruso S, et al. Quality of life and sexual function of naturally postmenopausal women on an ultralow-concentration estriol vaginal gel. 2016 Jan;23(1):47-54. doi: 10.1097/GME.0000000000000485.
  • [iii] Murina F, et al. Coital Pain in the elderly: could a low dose estriol gel thrill the vulva vestibule? Eur J Obstet Gynecol Reprod Bio 2016 Dec;207:121-124. doi: 10.1016/j.ejogrb.2016.10.016. Epub 2016 Nov 2.
  • [iv] Bussen, S et al, Comparison of Conservation and Surgical Therapy Concepts for Synechia of the Labia in Pre-Pubertal Girls. Geburtshilfe Frauenheilkd. 2016 Apr; 76(4): 390–395. doi:1055/s-0035-1558101.
  • [v] Ovestin cream (estriol). http://www.netdoctor.co.uk/medicines/a7950/ovestin-cream-estriol/. Accessed February 9, 2018.
  • [vi] Alliance for Natural Health USA. Access to Estriol. http://www.anh-usa.org/access-to-estriol-2/. Accessed February 9, 2018.
  • [vii] MSD Animal Health. Incurin product details. http://www.msd-animal-health.co.nz/Products/Incurin_/020_Product_Details.aspx. Last accessed: April 2018.
Vaginal Use of Estriol 2018-05-01T14:54:42+00:00

Hormones and Reproductive Health

Hormones and Reproductive Health

Written by Michelle Violi, Pharm.D. – Women’s International Pharmacy

 

Couple expecting babyWhat would we do without the human reproductive system? True, we might have fewer hormonal ups and downs, but it wouldn’t be long before humans would no longer populate the earth. Let’s take a closer look at how this very important system works in both women and men.

The Female Reproductive System

A woman’s reproductive system is delicate and complex. In order for conception to occur, it is important for a woman’s hormones to be balanced and her organs and tissues healthy. Hormones such as estrogen and progesterone play leading roles; however, there are many other hormones that are important players in the intricate process that is the female reproductive system.

Immediately following menstruation, estrogen levels begin to rise, causing the lining of the uterus to thicken. At ovulation an egg is expelled from the ovary into the fallopian tube where it travels to the uterus. After ovulation occurs, progesterone is produced from the corpus luteum, which forms in the ovary from which the egg was released.

Progesterone causes the uterine lining to become secretory and ready for the egg to implant should fertilization occur. If fertilization occurs, the fertilized egg implants in the uterine lining. The corpus luteum continues to produce progesterone until the placenta takes over its production in the second trimester of pregnancy. If fertilization does not occur, the corpus luteum breaks down, estrogen and progesterone levels fall, menstruation occurs, and the cycle begins anew.

The Male Reproductive System

A man’s reproductive system is no less complex. The primary hormones involved in the functioning of the male reproductive system are follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone.

FSH and LH are produced by the pituitary gland located at the base of the brain. FSH is necessary for sperm production (spermatogenesis), and LH stimulates the production of testosterone, which is necessary to continue the process of spermatogenesis. Testosterone also is important in the development of male characteristics, including muscle mass and strength, fat distribution, bone mass, and sex drive.

Hormonal Effects on Fertility

Infertility issues are very complicated and have many possible causes, including hormone imbalances or deficiencies. The following are just a few ways hormones play a role in fertility.

Hypothyroidism, or low thyroid function, can affect fertility due to menstrual cycles without ovulation, insufficient progesterone levels following ovulation, increased prolactin levels, and sex hormone imbalances. In a study involving 394 infertile women, 23.9% had hypothyroidism. After treatment for hypothyroidism, 76.6% of infertile women conceived within 6 weeks to 1 year.

Luteal phase deficiency (LPD) is a condition of insufficient progesterone exposure to maintain a normal secretory endometrium and allow for normal embryo implantation and growth. Progesterone is used in patients who experience recurrent miscarriages due to LPD. In addition, studies have shown progesterone can reduce the rate of preterm birth in certain individuals.

Conclusion

The human reproductive system is delicate, complex, and affects the overall health of women and men. Hormones serve an important role in maintaining harmony and promoting fertility in this intricate system. Because of this, achieving hormonal balance is a crucial component to supporting reproductive and overall health.

  • Lessey BA, Young SL. Yen & Jaffe’s Reproductive Endocrinology. 7th ed. Amsterdam, The Netherlands: Elsevier; 2014. https://www-clinicalkey-com.ezproxy.library.wisc.edu/#!/content/book/3-s2.0-B978145572758200010X?scrollTo=%23hl0000927 Accessed July 3, 2017
  • https://my.clevelandclinic.org/health/articles/the-male-reproductive-system Accessed July 3, 2017
  • Liedman R, Hansson SR, Howe D, et al. Reproductive hormones in plasma over the menstrual cycle in primary dysmenorrhea compared with healthy subjects. Gynecol Endocrinol. 2008;24:508-513. Accessed April 11, 2017.
  • Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011;38:18-31.
  • Barda G, Ben-Haroush A, Barkat J, et al. Effect of vaginal progesterone, administered to prevent preterm birth, on impedance to blood flow in fetal and uterine circulation. Ultrasound Obstet Gynecol. 2010;36:743-748.
  • Mesen TB, Young SL. Progesterone and the luteal phase. Obstet Gynecol Clin North Am. 2015;42(1):135-151.
  • Verma I, Sood R, Juneja S, et al. Prevalence of hypothyroidism in infertile women and evaluation of response of treatment for hypothyroidism on infertility. Int J Appl Basic Med Res. 2012 Jan-Jun; 2(1):17-19.
Hormones and Reproductive Health 2017-12-05T12:33:07+00:00

Ovulation is Crucial

Ovulation is Crucial to Women’s Health

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

ovulation is crucial to women's healthMany of us, including medical practitioners, think that if we are having monthly, regular periods, then our reproductive system is healthy. Dr. Jerilynn Prior believes we haven’t studied ovulation closely enough. She details her position in a series of newsletters from the Centre for Menstrual Cycle and Ovulation Research (CEMCOR). Dr. Prior estimates that, among regularly menstruating women whose cycles have been normal for 10-30 years after menarche (one’s first period), one third do not ovulate. She suggests that ovulation is “a missing link in preventing osteoporosis, heart disease and breast cancer.”

Let’s Start at the Beginning

Let’s refresh our memories with a little physiology review. Ovulation is the release of an egg from an ovary. Once the egg leaves the ovary, the corpus luteum (a temporary endocrine gland) forms in the ovary and begins to produce progesterone. The egg travels down the fallopian tube to the uterus where it can be fertilized by sperm. If fertilization does not occur, the egg is swept from the uterus along with the thickened lining of the uterus during a woman’s monthly period, also known as menstruation.

The release of the egg at mid-cycle and the formation of the corpus luteum are necessary for the abundant production and release of progesterone, which is the hallmark of the second half of the menstrual cycle known as the luteal phase.

As a young girl reaches menarche, estrogen influences her body. Breasts start to develop and body fat is redistributed, rounding the body’s contours gradually into a “womanly” shape. However, ovulation doesn’t start immediately and therefore, neither does the release of progesterone. It could be as long as a year before ovulation actually starts, and only after ten years does ovulation occur 95% of the time. One indicator that ovulation has begun, Dr. Prior explains, is the size of the areola around the nipple. When ovulation starts the areola becomes larger and darker.

Ovulation may be disturbed by stress, emotional upset, inadequate nutrition, and over-exercising without adequate food intake. Dr. Prior writes that there are two types of ovarian disturbances. One is an anovulatory cycle when no egg is released by the ovary. The other is luteal phase defect when an egg is released but there is insufficient progesterone produced by the corpus luteum in the ovary, leading to a shortened luteal phase. Both ovarian disturbances result in an inadequate production of progesterone.

Testing for Ovulation

No test actually “sees” the egg being released from the ovary, so medical practitioners have developed tests that use indirect methods to detect when ovulation has occurred.

  • One test requires a daily ultrasound of the ovaries to track the formation of the pre-ovulation cyst on the ovary and the eruption that occurs when an egg is released.
  • Another test involves taking a biopsy of uterine tissue, which can show cell proliferation caused by estrogen exposure and cells that have matured under the presence of progesterone.
  • Blood tests can verify that progesterone levels are rising to expected levels during the luteal phase.
  • Ovulation predictor kits, available online and at drug stores, test for a release of LH (luteinizing hormone) from the pituitary gland (a precursor to ovulation), but do not establish that ovulation has actually taken place.

In Dr. Prior’s studies, she documented the effectiveness of monitoring molimina to predict ovulation. Molimina is the set of symptoms that appear before the menstrual period that indicate ovulation has occurred. These symptoms include:

  • The onset of pain high up in the underarm region
  • Fluid retention
  • Mood sensitivity
  • Appetite increase

These symptoms may be mild and not reach the severity of PMS symptoms. Dr. Prior notes that nipple pain and general pain in the breast indicate high estrogen levels, but not necessarily ovulation. If a woman has no awareness of an oncoming period, ovulation has probably not taken place.

Another way to track ovulation is to monitor body temperatures first thing in the morning. The progesterone produced following ovulation acts on the hypothalamus and increases body temperature. Temperatures will be above average for 10-16 days if ovulation has occurred. To monitor body temperatures, use a digital thermometer to record readings every day. Add up all the temperatures for the month and divide by the number of days to get the average temperature, and then count how many days have been above average.

Ovulation and Our Health

Few researchers have tracked the effects of ovulation and its related hormones on the body over the course of a lifetime, but Dr. Prior shares findings from a number of studies addressing specific aspects of women’s health, as well as her conclusions from this information.

  • A recent study demonstrated that the greatest increases in bone density for young women don’t occur until about one year after menarche, when ovulation starts and progesterone is produced from the ovaries. Progesterone has been seen to be active at the bone building sites, the osteoblasts. On the other hand, menstrual cycles without ovulation, especially during the perimenopause years, may account for increased bone loss.
  • For many years, researchers have observed that both estrogen and progesterone can contribute to breast cell growth and proliferation. However, initial observations were usually only made over a day or two. After a few days in cell cultures, estrogen continues to stimulate cell growth, but progesterone contributes to breast cell maturation and differentiation. These mature cells are less prone to become cancerous in the presence of progesterone.
  • A common myth about heart disease is that it is the same disease in women as in men. For example, cholesterol levels in women do not appear to correlate with heart disease as they do in men, and taking a daily aspirin for preventing a heart attack may work for men but not for women. It was thought that estrogen prevented heart disease because HDL levels were increased with adequate estrogen levels, but repeated studies demonstrate that this is a myth.
  • Progesterone may affect heart health in a number of ways. It may decrease blood pressure, and it doesn’t appear to be associated with clot formation. While restriction of blood flow in the arteries can increase heart attack risk, progesterone may reduce this risk by increasing blood flow as well as or better than estrogen. Progesterone also appears to help prevent insulin resistance and obesity, two important cardiovascular risk factors. Cycles without ovulation and progesterone production, therefore, could be considered a risk for heart disease.

What can we do to support ovulation and progesterone production? Reducing stress and a healthy, balanced diet are good first steps. In order to detect if ovulation is occurring, monitor pre-ovulatory days for symptoms, chart morning temperatures, or use ovulation predictor kits. If ovulation isn’t occurring, progesterone levels may become depleted. In this case, progesterone may be supplemented to achieve optimal levels. Dr. Prior recommends 300 mg of progesterone used in a cyclic fashion (use for two weeks, stop for two weeks) to restore progesterone lost from lack of ovulation.

As it turns out, we can’t assume everything is well just because we are having a monthly period. Much is going on behind the scenes. However, as stated above, we can pay attention to what our body is trying to tell us. By listening to our body, we can keep our body strong and healthy for years to come.

Ovulation is Crucial 2017-12-12T15:35:51+00:00

Broccoli and Hormone Balance

Broccoli and Hormone Balance: The Connection to Estrogen

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

Did you wonder why, as menopause looms, health and wellness literature implores you to eat more broccoli? What does broccoli do? How much broccoli are we talking about? Do we have to eat it every day?

Broccoli seems to be the poster child for the entire brassica family, a type of plant in the mustard family. Brassica plants are also known as cruciferous vegetables because of their cross-shaped flowers. There are more than 375 types of these flowering plants, including many important food plants such as brown mustard, Brussels sprouts, cabbage, cauliflower, kale, kohlrabi, rape, rutabaga, and turnips.

Broccoli and Estrogen

Broccoli is connected to hormonal balance by its effect on how the body breaks down estrogen. Often we read that the body produces three estrogens: estrone, estradiol and estriol. While this is true, the dozens of estrogen metabolites the body creates as it breaks down these estrogens are often ignored. Let’s focus in on two of these: the metabolites of estrone called 2 hydroxyestrone (2-OHE1) and 16 alpha hydroxyestrone (16-αOHE1). The balance between these two metabolites is known as the 2:16 estrogen ratio.

The idea that adjusting estrogen metabolism to favor 2-OHE1 over 16-αOHE1 is beneficial has become popular, and many labs are able to test for these two hormones to compare them. While 2-OHE1 is thought to calm estradiol’s stimulatory effect on cells, 16-αOHE1 may provide the opposite effect, possibly stimulating estrogen-related cell growth. 16-αOHE1 also may be associated with genetic damage in cells, and some studies identified higher levels of 16-αOHE1 in breast cancer tissue and women with breast cancer when compared to healthy individuals. As part of his dissertation, “A Dietary Strategy to Reduce Breast Cancer Risk,” Dr. Jay Fowke was able to demonstrate that eating broccoli created a positive shift to 2-OHE1in healthy post-menopausal women. The daily intake was 500 grams or just over one pound of broccoli per day, with broccoli being eaten at two meals per day.

Broccoli Alternatives

You are not alone if you think a pound of broccoli per day is daunting, but there are a few possible alternatives:

  • Two important compounds are abundant in broccoli: diindolylmethane (DIM) and its precursor, indole-3-carbinol (I3C), both of which can have an impact on the metabolism of estrogens. These two compounds have been associated with a reduction in cancer and tumor cell growth. I3C and DIM appear to shift estrogen metabolism away from 16-αOHE1 and toward the more desirable 2-OHE1. Supplements containing these compounds may be an alternative to relying solely on broccoli to shift metabolism.
  • Another alternative to eating heaps of broccoli is supplementing with broccoli sprout extract. These supplements are readily available to purchase, or you can sprout your own seeds and eat them like alfalfa sprouts.

More about Broccoli

Another important component of broccoli is sulforaphane. Sulforaphane is being widely studied for its effectiveness in cancer, autism, schizophrenia, and more. An important detoxification molecule, sulforaphane may help with fatty liver disease and may enhance liver detoxification pathways, which are critical to metabolizing estrogens. Sulforaphane may also help with tissue damage known as oxidative stress, which is associated with aging and diabetes.

One caution about the use of broccoli comes from its effect on the thyroid. A steady diet of broccoli–or other members of the brassica vegetable group– eaten raw and in large amounts can have negative effects on thyroid function. Broccoli contains molecules called glucosinolates which may inhibit iodine uptake and thyroid hormone formation, particularly in the event of an existing iodine deficiency. Eating brassica vegetables in moderation, cooking them, and adequate iodine intake can reduce these effects.

Conclusion

Humans have evolved with our food sources for eons. Who first dared to eat broccoli? Who recognized that broccoli and the other brassica vegetables seemed to help with menopausal hormone changes? Who started recommending broccoli to family and friends? Thanks in part to these early innovators, today we have an abundance of studies relating to the specific molecules found in the brassica family of vegetables. We are starting to see the vast number of functions these foods have in the body. Food, it seems, really is our natural pharmacy. So eat up, and, as your mother always said, “Moderation in all things.”

Broccoli and Hormone Balance 2018-04-07T10:59:15+00:00

Healthy Sleep and Rest

Healthy Sleep and Rest

Written by Gina Besteman, RPh, & Michelle Violi, PharmD – Women’s International Pharmacy

One of the more common symptoms of peri-menopause and menopause that patients complain of is difficulty sleeping. There is a significant amount of research showing how hormones affect healthy sleep. healthy sleep

Progesterone affects GABA receptors which are responsible for non-REM sleep, the deepest of the sleep stages. Progesterone also affects breathing. It’s been shown to be a respiratory stimulant and has been used to treat mild obstructive sleep apnea.

The role of estrogen in sleep appears to be more complicated than that of progesterone. Estrogen is involved in breaking down norepinephrine, serotonin, and acetylcholine in the body. It has also been shown to decrease the amount of time it takes to fall asleep, decrease the number of awakenings after sleep occurs, and increase total sleep time. Low estrogen levels may lead to hot flashes, which can also affect sleep.

Cortisol is a hormone produced by the adrenal glands in response to stress. It normally peaks in the early morning followed by a slow decline throughout the day and night. However, chronic stress can alter healthy cortisol production and lead to sleep problems if cortisol is low in the morning and increased in the evening and at night.

Melatonin is a hormone produced by the pineal gland in the brain that regulates sleep and wakefulness. Normally, melatonin levels begin to increase in the mid to late evening, remain elevated throughout the night and drop in the morning. In general, melatonin levels decrease with age and melatonin production can be shut off by bright light. If melatonin levels are disrupted, sleep may be disrupted as well.

In addition to hormones, sleep can be affected by a number of external factors. It is important to maintain proper sleep hygiene as follows:

  • Avoid napping during the day
  • Avoid stimulants such as caffeine, nicotine, and alcohol too close to bedtime
  • Exercise can promote good sleep, but avoid vigorous exercise too close to bedtime
  • Food can be disruptive right before sleep
  • Ensure adequate exposure to natural light during the day
  • Establish a regular relaxing bedtime routine
  • Associate your bed with sleep
  • Make sure that the sleep environment is pleasant and relaxing and free from light pollution, e.g., lighted alarm clock faces, street lights through open windows, and cell phones/tablet devices
  • Eichling PS. Evaluating and Treating Menopausal Sleep Problems. Menopause Management. Sept/Oct 2002.
Healthy Sleep and Rest 2017-12-14T15:01:55+00:00

Book Review – Female Brain Gone Insane

Book Review – Female Brain Gone Insane by Mia Lundin, NP, RN

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

How many women have felt like her world was falling apart at some stage in her life? Assailed by symptoms such as anxiety, depression, sleep disturbances, irritability, weeping, brain fog, and loss of focus and concentration, she seeks help from her trusted medical practitioner. Traditional medicine offers her symptomatic relief with pharmaceutical chemicals such as anti-depressants, anti-anxiety agents, and sleep aids. Side effects from these medications sometimes lead to the addition of more medications. When this option fails, the medical practitioner, at a loss, may tell her, “It’s all in your head.” This roller coaster of symptoms can make any woman think she is going insane.

This happened to Mia Lundin, NP, author of Female Brain Gone Insane, after she gave birth to her second child. Although resistant, she did turn to antidepressants for a time. Prior to using antidepressants, she noticed an injection of progesterone dramatically relieved her symptoms for a few days. Ultimately, her curiosity about hormones, sparked by the benefit she experienced with progesterone, led her to a 20-year clinical practice using bioidentical sex, adrenal, and thyroid hormones along with amino acids to help with neurotransmitter production in the brain.

Neurotransmitters are made in the body from amino acids obtained by digesting proteins in the diet. Neurotransmitter balance is a key component of brain function. There are over 50 known neurotransmitters, but those we understand the best are serotonin, GABA, norepinephrine (or noradrenaline), and dopamine. The first two have calming effects and the second two are excitatory. Neurotransmitters do not operate alone, but are greatly influenced by sex, thyroid, and adrenal hormones.

A woman’s hormone levels may be especially affected at certain times during her life. Hormone fluctuations may occur cyclically before a woman’s period, after childbirth, and during perimenopause. Low hormone levels are common during perimenopause, menopause, and surgical menopause. These hormone level changes may produce changes to the hormone-brain chemistry balance.

Estrogen affects serotonin activity in a number of ways. Estrogen makes tryptophan, an amino acid precursor to serotonin, more available in the brain to make serotonin. Estrogen also supports serotonin levels by enhancing the removal of the enzyme, monoamine oxidase (MAO), that breaks down serotonin in the brain. Additionally, estrogen sensitizes serotonin receptors and fluctuating estrogen levels may impair the production of serotonin. Loss of the calming effect of serotonin may trigger symptoms of agitation, sensitivity, and uneasiness.

Adrenal cortisol may become depleted when the body is under continuous stress. When this happens, estrogen and progesterone can become unbalanced. GABA levels may be affected because progesterone stimulates GABA production. Serotonin stores may also become depleted.

On the other hand, if adrenaline and cortisol are high, as during a response to acute stress, and estrogen is out of balance with progesterone, thyroid activity may be inhibited. Low thyroid function can contribute to low serotonin levels and low serotonin levels can contribute to low thyroid function.

In Female Brain Gone Insane, Lundin does much more than describe how the disruption of hormones affects brain chemistry. She supplies lists of symptoms to help identify hormone deficiencies and excesses, provides suggestions on hormone testing and how to have it done, and she suggests ways to approach medical practitioners to find assistance with hormone use. She provides questionnaires and charts for those who want to help themselves. In short, she provides the framework for an entire lifestyle makeover. Women who feel that their world has fallen apart can find guidance back to themselves in this book.

This book is an excellent primer for those who want to learn more about bioidentical hormone therapies. Further, it is so well-referenced that practitioners who want to start learning about identifying and helping their patients with hormone-brain chemistry imbalances will find what they need here.

Book Review – Female Brain Gone Insane 2017-12-13T17:40:01+00:00

Vitamin K2 – A Missing Link in the Western Diet?

Vitamin K2 – A Missing Link in the Western Diet?

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

In 1925 an enterprising dentist, Dr. Weston Price, and his wife began traveling the world and documenting their observations of healthy, remote populations. They observed significant changes in tooth arrangement and mouth and facial structure when people of various cultures strayed from their traditional diet and adopted the Western diet. Traditional diets varied greatly, but all consisted of animal protein and fat in the form of fish, fowl, land animals, eggs, milk and milk products, reptiles, and/or insects. The Western diet introduced processed foods, sugar, and grains. Narrowed mouths, crowded teeth, thin faces, and smaller arches appeared in children whose parents adopted the Western diet. Dr. Price suspected that something specific was missing from the Western diet. He called this mysterious factor Activator X. He demonstrated that Activator X was prevalent in the meat and milk products of animals that grazed on green grasses. He even showed that these facial and dental abnormalities could be reversed in the next generation if Activator X was replaced in the diet. Finally, in 2006, Dr. Price’s Activator X was identified to be vitamin K2.

Confusion With the K’s
There are a number of types of vitamin K, but only two natural forms: vitamin K1 and vitamin K2. Vitamin K1 is present in leafy, green vegetables and is most identified with blood clotting. The drug, Coumadin, works to prevent blood from clotting by inhibiting the action of vitamin K1. The effects of excessive Coumadin may be reversed by administering vitamin K1.

Vitamin K2 exists in a number of distinct active forms. The two most commonly seen are designated as MK-4 and MK-7. MK-4 is present in the organs, milk, eggs and cheese of grass-fed animals. MK-7 is most abundant in a bacterial ferment of soy beans called natto. It is also present in lesser amounts in other fermented foods. Vitamin K2 does not appear to share Vitamin K1’s association with blood clotting.

A Calcium Paradox
Nutritional biochemistry is complicated. In order to learn how various vitamins and minerals work in the body, we often look at the function of one single nutrient at a time. However, when we do this, we fail to understand how nutrients work together. For example, we know that bones need calcium, but supplementing with calcium alone is unlikely to strengthen one’s bones. We need to consider how a number of nutrients work together to contribute to bone health. Each of the fat soluble vitamins, A, D, E, and K, works together synergistically. Vitamin D facilitates calcium absorption into the blood stream. Vitamin K2 converts vitamin D into its active form and also activates the hormone osteocalcin to direct the calcium to the bone. A deficiency of any one of these vitamins may cause malfunctions in the body. Specifically, a deficiency of vitamin K2 may cause calcium to be stored in other tissues rather than being directed to the bone. If calcium settles in the arteries, it can lead to atherosclerosis. Calcium may also cause problems by settling in the joints and in soft tissues like the breasts.

The French Paradox Solved?
Many find it surprising that the French eat a lot of cholesterol and saturated fat and have low rates of death from coronary heart disease (CHD). Some think it’s an ingredient in red wine that keeps them healthy. Perhaps these saturated fats laden with vitamin K2 are the protective factor.

Vitamin K2 in All Parts of the Body

  • Heart Disease: One of the most powerful tools against calcification of the blood vessels is a vitamin K2 activated protein.
  • Osteoporosis: Vitamin K2 activated osteocalcin directs calcium to the bones.
  • Diabetes and Metabolic Syndrome: Vitamin K2 improves insulin sensitivity thus potentially stalling progression to metabolic syndrome and diabetes.
  • Wrinkles and Tissue Laxity: May be due to a vitamin K2 deficiency causing misplaced calcium in the skin and tissues.
  • Varicose Veins: May be due to a vitamin K2 deficiency causing calcium to deposit in the veins.
  • Arthritis: Joint damage may reflect a vitamin K2 deficiency.
  • Dental Health: Vitamin K2 may be useful in treating and preventing dental cavities.
  • Pregnancy: Adequate vitamin K2 promotes the healthy development of fetal teeth and facial structure. Also, labor may be easier when vitamin K2 levels are adequate.
  • Cancer: Vitamin K2 promotes cell differentiation and may protect against metastasis.
  • Nervous System: Vitamin K2 plays a role in nervous system protection, myelin development, and signal transduction.

Vitamin K2 and Hormones
Vitamin K2 has an important relationship with estrogen and bone health. Estrogen and bone density both decline during menopause and postmenopausal women are often markedly deficient in vitamin K2. Bone health may be improved in postmenopausal women by restoring adequate vitamin K2 levels as vitamin K2 acts in the bone loss pathway in a number of areas specific to the loss caused by low estrogen levels. Vitamin K2 also plays a role in estrogen metabolism itself. Additionally, testosterone levels and sperm production may be improved by osteocalcin, the hormone activated by vitamin K2.

Conclusion
It is remarkable that it took decades from Dr. Weston Price’s careful observations and characterization of Activator X to finally identify vitamin K2 and a number of its myriad functions. We are still not sure of the appropriate supplement dose to use or the amount of vitamin K2 rich foods to eat. Tests are being devised to help evaluate our vitamin K2 status. In the near future, we will be able to measure vitamin K2 levels as readily as we test for vitamin D now. Research has only scratched the surface of the potential of this fascinating vitamin!

Vitamin K2 – A Missing Link in the Western Diet? 2018-04-05T11:10:21+00:00

Hormones for Hot Flashes

Hormones for Hot Flashes

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

The FDA approved the first and only non-hormonal treatment for hot flashes in 2013. Brisdelle (paroxetine) belongs to a class of drugs called selective serotonin reuptake inhibitors (SSRIs). These medications are used primarily to treat depression. Before Brisdelle was approved, estrogens were the only FDA-indicated treatment for hot flashes.

A new study highlights an increased risk for bone fractures in women taking SSRIs for non-psychiatric conditions like hot flashes. Statistics from an insurance claims database indicate that female patients, aged 40-64 without mental illness who started SSRIs from 1998-2010, had an increased risk of breaking a bone compared to a similar group that started using proton pump inhibitors for stomach disorders. It may be time to reevaluate the use of SSRIs for the treatment of hot flashes.

Estradiol is FDA-approved for the treatment of hot flashes as well as for the prevention of osteoporosis. Misinterpretation of the Women’s Health Initiative (WHI) Study has generated apprehension regarding the use of bioidentical hormone replacement therapy (BHRT) for hot flashes.

Dr Kent Holtorf has reviewed numerous published papers and concluded that BHRT is safer and more effective than conventional hormone replacement therapy. Individualizing therapy and balancing hormone benefits vs risks is the key to successful management of menopausal hot flashes. There is no need to substitute an SSRI for the real-deal.

Read more in the Women’s International Pharmacy Connections Newsletter on Menopause.

  • Sheu YH, et al. SSRI use and risk of fractures among perimenopausal women without mental disorders. Inj Prev. 2015 Jun 25. doi: 10.1136/injuryprev-2014-041483. (Epub ahead of print)
  • Holtorf K. The Bioidentical Hormone Debate:  Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy? Postgrad Med. 2009 Jan;121(1):1-13.
Hormones for Hot Flashes 2017-12-13T15:20:48+00:00

Adrenal Estrogens

Adrenal Estrogens: Are we missing something?

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

 

Dr. Al Plechner, veterinarian, has authored books about the importance of cortisol produced by the adrenal glands in preventing allergies, autoimmunity, and cancer. Citing Dr. William McK. Jefferies’ classic book, Safe Uses of Cortisone, Dr. Plechner stresses that low cortisol production by the body due to stress, lack of exercise, poor nutrition, and other factors contributes to the same conditions in humans as it does in animals.

Low levels of cortisol in the body cause the pituitary gland in the brain to produce more and more ACTH (adrenocorticotropic hormone) in an attempt to stimulate the adrenal glands to make more cortisol. However, when the adrenal glands are fatigued and unable to produce more cortisol, the continuous stimulation of the adrenal glands by ACTH causes them to produce estrogens and androgens like DHEA instead.

Dr. Plechner maintains that estrogens produced by the adrenal glands contribute to inflammatory diseases. He suggests that we measure total estrogen levels in the body to see the entire picture. If a practitioner only measures estradiol levels and then supplements with estrogen when the estradiol levels are low, this could lead to an excess in total estrogen levels in the body leading to problems resulting from too much estrogen.

As more men and women turn to testosterone supplementation, Dr. Plechner reminds us that we should pay attention to the aromatization (conversion) of testosterone to even more estrogen. He recommends measuring total estrogen levels in both women and men prior to supplementation with testosterone to avoid potential complications resulting from excess estrogen.

  • Plechner A. Elevated Estrogen is Feared by the Medical Profession; However the Medical Profession Does Not Measure Total Estrogen. Townsend Newsletter. 2015 April: 79-80. www.drplechner.com.
  •  Jefferies WM. Safe Uses of Cortisol. Springfield, IL: Charles C Thomas; 2004.
Adrenal Estrogens 2017-12-08T12:37:49+00:00