Adipose Tissue during Menopause

Adipose Tissue Distribution during Menopause

Balancing Hormones to Control Body Fat, Prevent Chronic Disease, and Achieve Healthy Aging

Written by Athena Parmenter, PharmD, MA – Women’s International Pharmacy

The aging process is naturally accompanied by an increase in body fat, or adipose tissue. Excess adipose tissue—particularly in the abdominal area—may lead to increased inflammation in the body, resulting in a greater risk of certain diseases such as:

  • Type 2 diabetes
  • Metabolic syndrome
  • Atherosclerosis
  • Cardiovascular disease

However, this harmful increase in adipose tissue mass may be partly reversed by hormone replacement therapy (HRT) during the peri- and postmenopausal periods.

Declining estradiol levels during menopause cause fat distribution to shift from the hips and thighs to the abdomen. Studies have shown that estradiol also has anti-inflammatory properties; this may be one reason why the risks of the aforementioned chronic diseases are much lower before menopause. As estradiol decreases and the amount of adipose tissue increases, many substances that promote inflammation (such as cytokines and adipokines) increase.

A subanalysis within the Women’s Health Initiative (WHI) showed that HRT “significantly reduced both the loss of lean soft tissue mass and the ratio of trunk to leg fat mass in postmenopausal women.” In other words, women who used HRT had smaller waists when compared to their legs than the women who did not use HRT. Although this study was conducted using synthetic estrogens and progestins, it would not be unreasonable to extend its conclusions to bioidentical hormone therapy as well.

Hormonal imbalance during menopause may contribute to many health conditions normally associated with aging. Among these physical changes, adipose accumulation may lead to more serious health concerns caused by inflammation. With its potential to help maintain healthy fat distribution, HRT may be able to play a role in slowing the progression toward these age-related chronic diseases.

Adipose Tissue during Menopause2019-09-25T10:32:24-05:00

Book Review – Hair Like a Fox by Danny Roddy

Book Review – Hair like a Fox by Danny Roddy

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

Men and women alike have issues with hair loss. Is this natural? Is this normal? For Danny Roddy, author of Hair like a Fox: A Bioenergetic View of Pattern Hair Loss, fear of hair loss was imprinted in his childhood. At the age of 19, he made it a personal challenge to learn about hair loss and do all that he could to keep his hair. As he had feared, Roddy did begin losing hair despite his efforts. It was only by discovering the work of Dr. Ray Peat that Roddy finally found a new perspective on the underlying cause of hair loss and how it may be prevented.

Conventional Theories of Hair Loss Causes

The Androgen Hypothesis

Let’s examine the history first. In the 1940s, Dr. James B. Hamilton published his observations of 104 men without functioning testicles. He found these men did not mature sexually and had altered hormone levels. They also retained their scalp hair, had reduced oiliness of the scalp, and little to no dandruff.

Seeing this connection, Dr. Hamilton administered testosterone to men without functioning testicles who were not bald but who had a family history of baldness. Soon they experienced hair loss, which abated when the treatment stopped. When the testosterone was later resumed, balding proceeded again. Dr. Hamilton concluded that baldness was caused by androgens, specifically testosterone.

In the 1970s Dr. Julianne Imperato-McGinley studied a population in a remote area of the Dominican Republic who were born with ambiguous sexual features. From birth and throughout their childhood, these individuals appeared to be girls. At puberty, however, they developed male sex organs.

These men had no signs of baldness, had small prostate size, and normal testosterone levels. However, they lacked the enzyme needed to convert testosterone to its stronger metabolite, dihydrotestosterone (DHT). Dr. Imperator-McGinley became convinced that DHT—not testosterone— was responsible for male pattern baldness.

Merck and Finasteride

Merck scientists became aware of Dr. Imperato-McGinley’s research and developed a drug which would block the production of DHT. The result was finasteride. Finasteride not only reduced symptoms and helped shrink the prostate in men with enlarged prostate glands, but incidentally contributed to regrowth of hair as well.

According to Roddy, finasteride may have enough progesterone activity to help with hair loss–at least part of the time. This new treatment was not without drawbacks, however: Large numbers of men suffered side effects such as erectile dysfunction, lack of libido, depression, and suicide. In addition, finasteride was not the total answer for the hair problem, either, as it was only effective for about 40% of the men who took it.

The Androgen Hypothesis Falls Apart

Why do young men with the highest testosterone and DHT have the best hair? Why does balding occur when the hormone levels are dropping with age? Why do women experience “male” pattern baldness? Medical practitioners tend to cling to explanations involving DHT or genetics in spite of the holes in these theories.

Dr. Peat and the Hair Follicle as a Mini Organ

Dr. Ray Peat is a prolific writer and thinker, and often challenges conventional thinking. Perhaps best known for his foundational research on progesterone, Dr. Peat’s work directs one to consider the hair follicles as mini organs.

Like other organs in the body, hair follicles depend upon the energy of the cells in their structure, and this cellular energy is produced by mitochondria. With time, stressors may diminish the function of the cells; hair follicles become clogged with mucopolysaccharides (mucin), calcification, impaired blood flow leading to low available oxygen, oxidative stress and finally, impaired function of the mitochondria.

Active Thyroid Hormone (T3)

Mitochondria need glucose and oxygen to produce energy. We get glucose with carbohydrates, but our bodies can also convert it from protein. Even more than glucose, however, energy production relies upon oxygen sources. A byproduct of cell energy production is carbon dioxide, which helps move oxygen from the blood and into the tissues and cells.

Active thyroid hormone (T3) stimulates the use of oxygen in breaking down the carbohydrates, fats, and proteins. This, in turn, yields carbon dioxide, which improves the oxygen transport to the cell. In individuals with low thyroid levels, the body produces mucin, a gelatinous substance that solidifies in the spaces between cells. When mucin becomes calcified it cuts off circulation to the scalp. Hairs become progressively wispier until the hair follicle is choked off entirely.

Graying and loss of hair are symptoms of declining mitochondria function, and thus loss of cell energy. If proper cell metabolism is compromised, functioning in all parts of the body is slowed down. Declining cell energy may be linked to a wide variety of diseases, such as:

  • Alzheimer’s
  • Atherosclerosis
  • Autism
  • Cancer
  • Chronic fatigue
  • Fibromyalgia
  • Heart failure
  • Epilepsy
  • Hypertension
  • Hypoglycemia
  • Depression
  • Infertility
  • Migraines
  • Non-alcoholic liver disease
  • Obesity
  • Sleep apnea
  • Diabetes
Estrogen (and Other Hormones) Can Cause Hair Loss

Progesterone depends upon thyroid function. If estrogen is not balanced by plenty of progesterone, hair loss may result. During menopause, progesterone levels decline while estrogen activity soars. Relatively high levels of estrogen may, in turn, also inhibit progesterone production, creating a vicious cycle.

Hair is affected by other hormones as well. The pituitary hormone prolactin increases with age in men and may inhibit hair growth. Cortisol levels from the adrenal glands increase with aging and may contribute to hair loss.

As it happens, not only do men without functioning testicles have low testosterone levels, but they are also low in estrogen. Perhaps the lack of this hormone further inhibits hair loss for them.

Conclusion

Hair Like a Fox contains many more chapters discussing serotonin, essential fatty acids, types of carbohydrates, proteins, and fats that produce cellular energy and contribute to hair growth. Rather than the simple cause-and-effect theory of androgen-induced baldness, the real key to maintaining hair follicle structure may be to maintain mitochondrial health. Optimizing how the body can best produce cell energy applies to every cell in the body, not just the tiny hair follicle organ. This may be a remedy for not only defying hair loss but also resisting those diseases associated with aging.

Additional Resources:

If you are wondering how Danny Roddy and his hair are doing, check out his blog at www.dannyroddy.com. This website is rich with information, but Roddy feels the quest is not over yet and there is always more to learn.

  • Roddy D. Hair Like a Fox: A Bioenergetic View of Pattern Hair Loss. The Danny Roddy Weblog, LLC: 2013. https://www.amazon.com/Hair-Like-Fox-Bioenergetic-Pattern-ebook/dp/B00GYX6QXC.

© 2019 Women’s International Pharmacy

Edited by Michelle Violi, PharmD; Women’s International Pharmacy

For any questions about this article, please e-mail

Carol Petersen at carol@womensinternational.com

Book Review – Hair Like a Fox by Danny Roddy2019-07-05T12:21:19-05:00

How Do Hormones Affect the Heart?

How Do Hormones Affect the Heart?

Written by Michelle Violi, PharmD – Women’s International Pharmacy

“How does hormone supplementation affect the heart?” This is a question that our pharmacists hear regularly. Much like the poor, maligned egg in the cardio-healthy diet, hormones have fallen in and out of favor with regard to their effect on the cardiovascular system over the years.

Although a number of studies examine hormonal effects on the cardiovascular system, these studies rarely distinguish between bioidentical and synthetic hormones. However, one study by Dr. Ferdinand Roefsena, Rebecca J. Yang, and Dr. Johannes Veldhuis looked specifically at the bioidentical hormones, estradiol, and progesterone, publishing their results in the Journal of the Endocrine Society. Let’s see what they found!

How Was the Study Designed?

Forty healthy postmenopausal women, ages 50-80, participated in the study. The women were divided into four treatment groups:

  1. Bioidentical estradiol (injection) and bioidentical progesterone (by mouth)
  2. Bioidentical estradiol (injection) and no bioidentical progesterone
  3. Bioidentical progesterone (by mouth) and no bioidentical estradiol
  4. No bioidentical estradiol and no bioidentical progesterone

After 23 days of using these therapies, the women’s blood was drawn and the researchers measured various markers.

What Did the Study Look At?

Because the study was only 23 days long, Dr. Roefsena et al. were unable to evaluate primary endpoints, such as heart attacks or strokes. Instead, they looked at various markers in the blood that have been associated with physical outcomes such as heart disease, stroke, and diabetes. The researchers looked at many significant markers, including:

  1. Total cholesterol
  2. Low-density lipoprotein cholesterol (LDL-C) (referred to as “bad” cholesterol by the American Heart Association)
  3. High-density lipoprotein cholesterol (HDL-C) (referred to as “good” cholesterol by the American Heart Association)
  4. Apolipoprotein B (Apo B)
  5. High sensitivity C-reactive protein (hsCRP)
  6. Adiponectin

With the exception of HDL-C and adiponectin, for which higher levels appear beneficial, decreased levels of the other markers listed above are generally considered favorable, according to the American Heart Association.

What Did the Study Find?

When compared to women who weren’t using any hormone therapies:

  1. Women who used bioidentical estradiol alone had lower levels of total cholesterol, LDL-C, and Apo B. They also had higher levels of HDL-C, which are considered beneficial differences. The researchers had expected this result, based on previous studies as described in the article The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy? by Dr. Kent Holtorf.
  2. Women who used bioidentical progesterone alone had decreased adiponectin, but they were still well within the average reference range (below which would indicate risk).
  3. Women who used bioidentical estradiol and bioidentical progesterone together had lower levels of total cholesterol, LDL-C, Apo B, and HDL-C. While the reduced HDL-C levels are not considered beneficial, other studies, as discussed in Dr. Holtorf’s article, indicate that when synthetic progestins are used instead of bioidentical progesterone, the cholesterol and LDL-C-lowering effect of bioidentical estradiol is also blocked. Bioidentical progesterone did not block this effect!
  4. hsCRP levels were higher in women using bioidentical estradiol and bioidentical progesterone, but still well below the value above which indicates increased risk.

In Summary:

As the researchers expected, the women using bioidentical estradiol exhibited improved cholesterol levels (including decreased LDL-C and increased HDL-C). Even though the bioidentical progesterone was associated with reduced HDL-C levels, it allowed the positive effects of bioidentical estradiol on the other cholesterol levels to remain. Synthetic progestins have been seen to reduce the positive effects of bioidentical estradiol on cholesterol levels, as evidenced by the studies discussed in Holtorf’s article. These findings suggest that bioidentical hormones may be preferable to synthetic.

This study is not without its flaws, such as its short length and small group size. Its short length made it necessary to evaluate markers rather than primary endpoints, and the data was further limited by comparing the groups to each rather than evaluating the differences between the beginning and ending measurements. The patients in the bioidentical estradiol groups were treated with injectable bioidentical estradiol—a form which is rarely used in clinical practice—and used two doses ten days apart as opposed to the usual two- to four-week intervals.

Despite this study’s shortcomings, when we combine its results with information obtained in other studies, we see that bioidentical progesterone doesn’t appear to interfere with the positive effects estrogen has on cholesterol levels. By contrast, other studies have suggested that synthetic progestins do negate these effects. And this makes perfect sense! Why would we assume that a molecule that is similar, but not identical to what the body makes, should have the same effect in the body as a molecule that is identical to what the body makes?

Due to our differences as individuals, no study is perfect. Therefore, the question of whether hormones are good for your heart may never be answered definitively because the answer may differ from person to person. Through studies like that by Dr. Roefsena et al. and others, however, one thing is becoming clear: the difference between bioidentical and synthetic hormones may prove a significant factor in whether hormones are beneficial to the heart.

Additional Resources:

Women’s International Pharmacy has several other articles focused on how hormones affect heart health. Check them out at our Heart Health Resources page!

© 2019 Women’s International Pharmacy

Reviewed by Carol Petersen, RPh, CNP; Women’s International Pharmacy

How Do Hormones Affect the Heart?2019-03-14T12:28:58-05:00

Book Review – Estrogen’s Storm Season

Book Review – Estrogen’s Storm Season: Stories of Perimenopause by Dr. Jerilynn Prior

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

stormDr. Jerilynn Prior is a Professor of Endocrinology and Metabolism at the University of British Columbia in Vancouver. She is also the Scientific Director of the Centre for Menstrual Cycle and Ovulation Research (CeMCOR).  Not only is Dr. Prior a dedicated scientist and medical writer, she has now turned to fiction to share her knowledge about women’s health. She knows from experience that it can take decades to disseminate information to those who would benefit the most. In Estrogen’s Storm Season she uses storytelling to carry her message by personifying the main challenges of perimenopause.

Perimenopause begins when the first symptoms appear and lasts until one year after the last menstrual cycle. In her book, Dr. Prior carefully documents the stages of perimenopause. Through fictional encounters with women going through perimenopause, she weaves useful information and helpful hints and concepts into her writing so that readers may be able to identify what is happening in their own lives. Here are the main symptoms she brings into focus:

  • Night sweats and hot flashes
  • Menorrhagia or heavy bleeding
  • Nausea
  • Infertility
  • Migraine headaches
  • Moodiness
  • Weight gain
  • Breast tenderness, pain, and swelling

While touching on these issues with broad strokes, she illustrates that life can be messy, as many other issues are entwined in her characters’ lives. Their concerns include high blood pressure, diabetes, heart disease, osteoporosis, and cancer. She also addresses the stress of work situations, relationships, financial concerns, and diet. Like real women, her characters discover that their discomforts and health concerns may be part of a bigger picture, and that solutions should be comprehensive, addressing health concerns and lifestyle modifications in addition to perimenopausal symptoms.

Many individuals may be unaware of an underlying theme of perimenopause, which Dr. Prior reveals in this book. Perimenopause has long been characterized as the time of life when women experience a decline in estrogen production. Dr. Prior claims this is not so; in fact, she has found in her studies that women experience the highest estrogen levels in their entire lifetime during perimenopause. In her opinion, too many women are prescribed estrogens (or birth control pills containing estrogens) when they are already suffering from too much estrogen. According to Dr. Prior, the hormone that is in decline is actually progesterone, which is needed to offset the effects of high estrogen levels. Dr. Prior has found success in progesterone treatments in tandem with employing a whole spectrum of life enhancements.

As her fictional characters come alive, Dr. Prior teaches women how to document their initial symptoms and their interventions with any subsequent symptom changes so that they can see for themselves what works and what doesn’t. These tools are available on the CeMCOR website, which overflows with practical information about the menstrual cycle as well as addressing questions and concerns a woman may have throughout her lifetime. Through Estrogen’s Storm Season, Dr. Prior’s guidance and understanding empowers women to take charge of their health.

Updates as of August 8, 2018:

The electronic version of the second edition of Estrogen’s Storm Season is available to download at the following additional sites:

Recent revisions to the print version of Estrogen Storm Season are posted to the Cemcor.ca site:

Additional Resources:

Book Review – Estrogen’s Storm Season2018-08-08T15:09:01-05:00

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

Vaginal Use of Estriol

Vaginal Use of Estriol

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

Estriol 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 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). https://www.netdoctor.co.uk/medicines/a7950/ovestin-cream-estriol/. Accessed February 9, 2018.
  • [vi] Alliance for Natural Health USA. Access to Estriol. https://www.anh-usa.org/access-to-estriol-2/. Accessed February 9, 2018.
  • [vii] MSD Animal Health. Incurin product details. https://www.msd-animal-health.co.nz/Products/Incurin_/020_Product_Details.aspx. Last accessed: April 2018.

© 2018 Women’s International Pharmacy

Reviewed by Michelle Violi, PharmD; Women’s International Pharmacy

For any questions about this article, please e-mail

Carol Petersen at cpetersen@womensinternational.com

Vaginal Use of Estriol2018-12-14T12:08:39-05:00

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 Health2017-12-05T12:33:07-05:00

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 Crucial2017-12-12T15:35:51-05:00

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 Balance2018-04-07T10:59:15-05:00

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 Rest2017-12-14T15:01:55-05:00