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PCOS and Hormones

Polycystic Ovary Syndrome and Hormones

How Testosterone, Insulin, and Progesterone Affect PCOS

Written by Hershil Parekh, RPh – Women’s International Pharmacy

woman holding flower basketHave you struggled with excessive hair growth and acne, difficulty getting pregnant, weight gain, and chronic menstruation irregularities for most of your life? If you answered “Yes” to any of the above symptoms, you may be one of the 4-8% of women across the globe who suffers from Polycystic Ovary Syndrome (PCOS). It is often considered to be the most common endocrine disorder suffered by women of childbearing age in the United States. With no clear underlying cause, PCOS is a complex disorder encompassing many organ systems.

PCOS is usually diagnosed when a patient exhibits one or more the following symptoms:

  • High circulating testosterone levels
  • The presence of ovarian cysts (though contrary to what the name “Polycystic Ovary Syndrome” suggests, it’s possible to have PCOS without ovarian cysts)
  • Menstrual irregularities that lead to the inability to ovulate

Imbalances of the hormones testosterone, insulin, and progesterone play a critical role in the various symptoms of PCOS and the other conditions that may be associated with it. Managing PCOS involves treating these symptoms with lifestyle modifications and medications.

Understanding the HPG Axis and Its Role in Fertility

Regulation of the reproductive system starts in the hypothalamic-pituitary-gonad (HPG) axis. The HPG axis begins with the hypothalamus producing gonadotropin-releasing hormone (GnRH), which is then released in pulses to hormone receptors on the anterior pituitary gland. Depending on the rate of stimulation it receives, the anterior pituitary gland produces one of two gonadotrophic hormones: follicle stimulating hormone (FSH) or luteinizing hormone (LH).

  • During a woman’s menstrual cycle, FSH plays a key role in the growth and maturation of the ovarian follicle (a small fluid-filled sac in the ovary containing an immature egg) and estradiol production.
  • LH is responsible for the rupture of the mature ovarian follicle which releases an ovum for fertilization as well as the production of estradiol (in the first two weeks of the cycle) and testosterone and progesterone.

Abnormalities in LH and FSH production may lead to the inability to ovulate and also increases in testosterone production and decreases in progesterone production.

Hormonal Influences on PCOS Symptoms

Many of the problems associated with PCOS revolve around hormonal imbalances of testosterone, insulin, and progesterone.

PCOS and Testosterone

Testosterone is one of the many sex hormones made via the HPG axis and is considered an androgenic sex hormone. Androgens (from the Greek andro, meaning “male”) are found in higher concentrations in men than in women, and play a role in the development of male characteristics. Testosterone is produced when the reproductive system is stimulated by LH.

PCOS patients present with many adverse reactions associated with abnormally high testosterone levels:

  • Hirsutism (the growth of long, coarse, dark hair), develops in androgen-sensitive areas such as the chest, upper lip, chin, back, and abdomen.
  • Acne is caused in these androgen-sensitive areas when sebaceous glands in the skin begin to overproduce sebum (an oily substance secreted to moisturize the skin).
  • In hair follicles on the scalp, testosterone is broken down into dihydrotestosterone and results in male-pattern balding.

Another hormone called insulin exacerbates these symptoms when not utilized properly by the body.

PCOS and Insulin

Insulin is a metabolic hormone that helps the body exploit its main fuel source, glucose. PCOS patients commonly suffer from a weight-related metabolic condition called insulin resistance, where the body is not sensitive to insulin spikes after the consumption of food. Insulin is needed to help glucose penetrate cells of the body from the blood.

Poor utilization of insulin increases its levels in the blood and this may lead to increased testosterone in several ways:

  • Insulin may promote GnRH production in the hypothalamus, causing a more frequent stimulation of the anterior pituitary gland, which increases LH levels.
  • Insulin may also directly stimulate cells in the ovaries to produce more androgens.

Insulin may indirectly reduce transport proteins (called sex hormone binding globulin) which shuttle testosterone in the body. This increases the free testosterone that is available to circulate and activate receptors anywhere in the body and amplifies the testosterone response throughout the body.

PCOS and Progesterone

Dr. Jerilynn Prior, a Professor of Endocrinology and Metabolism, has spent her career studying menstrual cycles and the effects of the cycle’s changing estrogen and progesterone hormone levels on women’s health. She explains:

Progesterone is the hormone made by the ovary after an egg is released. Patients with [PCOS] have sporadic or absent ovulation, so they are not making progesterone for two weeks every cycle. This lack of progesterone leads to an imbalance in the ovary, causes the stimulation of higher male hormones, and leads to irregular periods and trouble getting pregnant. Progesterone is usually missing—replacing it therefore makes sense.

In an article for Gynecological Endocrinology, Dr. Helen Buckler et al. write that progesterone appears to normalize the heightened LH levels associated with PCOS. Raised LH is one of the mechanisms that stimulate testosterone production. In addition, Dr. Prior notes that progesterone inhibits the enzyme that allows testosterone to convert into dihydrotestosterone, the androgen that contributes to acne, hirsutism, and (as mentioned previously) male pattern baldness.

Treatment Options for PCOS

Multiple treatment options are available to control PCOS symptoms. Traditionally, PCOS has been treated with an array of medications that inhibit androgen hormones through various mechanisms. However, using progesterone in bioidentical hormone therapy is one alternative that replenishes progesterone levels and encourages the regulation of androgen production in a way more natural to the body.

Traditional Treatments

  • The anti-diabetic agent Metformin and a class of cholesterol-lowering medications called statins may be used for managing metabolism.
  • Anti-androgens (such as finasteride) may be used to control circulating testosterone levels and hirsutism.
  • Patients experiencing irregular menstrual cycles may be prescribed oral contraceptives containing progestins. However, synthetic progestins themselves may have negative effects on a woman’s health.
  • Clomiphene citrate may be used to induce ovulation in patients who are having difficulty getting pregnant.

Alternative Therapies

  • Compounded bioidentical progesterone may have a variety of benefits in the treatment of PCOS and its symptoms. According to Dr. Prior, progesterone signals to the HPG axis when to stop production of androgens, which prevents testosterone overproduction. If progesterone deficiency is addressed by supplementing compounded bioidentical progesterone for two weeks every month, it “may help the brain develop the normal cyclic rhythm that is missing in PCOS.”
  • Weight reduction with the help of a calorie-restricted diet and exercise is recommended to help decrease androgen levels and control glucose and insulin levels.

Conclusion

Controlling PCOS often requires a multifaceted approach. Treating individual symptoms decreases the development of associated conditions such as type 2 diabetes, cardiovascular disease, infertility, and endometrial cancer. Meanwhile, a combination of medications and healthy lifestyle habits may be used to address any underlying hormone imbalances that may exacerbate PCOS in the first place.

Additional Resources:

PCOS and Hormones2019-04-30T16:34:41-05:00

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

How Is the Thyroid Gland Like a Car?

How Is the Thyroid Gland Like a Car?

Understanding the Complexities of Treating Thyroid Dysfunction

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

car driving through a forestThe thyroid gland is a butterfly-shaped gland located in the front of the neck. It is responsible for producing hormones, which are essential for normal growth and development as well as regulating metabolism. Thyroid hormone function has been found to correlate with body weight and energy expenditure.

The thyroid gland produces two main hormones: levothyroxine (T4) and liothyronine (T3). T4 is an inactive thyroid hormone that must be converted to the active thyroid hormone, T3, before it can be used by the body.

Health care practitioners use testing and symptom evaluation to determine whether a patient’s thyroid gland isn’t working as it should. If the results indicate low thyroid function (hypothyroidism), there are a number of options they may prescribe:

Type of Thyroid PrescriptionExamples of Medications
Levothyroxine (T4) Only
  • Synthroid
  • Levoxyl
  • Compounded capsules
Liothyronine (T3) Only
  • Cytomel
  • Compounded capsules
A Combination of Liothyronine (T3) and Levothyroxine (T4)
  • Thyrolar (as of this writing in January 2019, on long-term back order)
  • Compounded capsules
Desiccated Porcine Thyroid

Taken from the thyroid gland of the pig, this contains T3 and T4, as well as thyroid cofactors such as T1, T2, calcitonin, and trace amounts of iodine

  • NatureThroid
  • Westhroid
  • WP Thyroid
  • Armour Thyroid
  • NP Thyroid
  • Compounded capsules

Levothyroxine (T4) only is the most commonly prescribed thyroid medication. However, this might not be the right choice in every situation. Because the thyroid gland plays a complex role in the body, some cases of thyroid dysfunction may require more than a “one medication fits all” approach.

Compare thyroid dysfunction to a car. When a car stops running, is it because it’s out of gas? Perhaps. In this case, fill up the tank and get back on the road. However, think of all the other possible reasons the car may have stopped running. The car may not be able to use the gas put in it or not use it well depending on whether the car needs diesel, premium, or regular. The car may be full of rust. The car may need oil or antifreeze, not gas. The list goes on and on.

In the case of thyroid function, there are also a wide variety of reasons why a thyroid gland may not be working. The thyroid gland may not be able to convert T4 to T3. The thyroid gland may be inflamed or be the target of an autoimmune response. The thyroid gland may need iodine, selenium, zinc, or other cofactors. As with a car, the list goes on and on.

If a patient with hypothyroidism is prescribed T4 only, the body must be able to convert T4 into T3 in order for the body to be able to use it. However, if there is an issue with this conversion process, the body may not be able to use a T4 only medication appropriately. Depending on what is wrong with the thyroid gland, additional support in the form of T3 or other thyroid cofactors such as are present in desiccated porcine thyroid may be needed.

As with so many things relating to health, optimizing thyroid function is complicated. If you are taking thyroid medication and still aren’t feeling well, don’t give up! Work with your health care practitioner and pharmacist to find a solution that fits your individual needs.

Additional Resources:

For more information on the thyroid gland, hormones, and treatments, visit our Thyroid Resources page.

How Is the Thyroid Gland Like a Car?2019-01-25T11:18:05-05:00

Could Red Wine Prolong the Effects of Testosterone?

Could Red Wine Prolong the Effects of Testosterone?

Written by Hershil Parekh, RPh – Women’s International Pharmacy

red wine may help testosterone functionDoes that glass of red wine you enjoy with dinner affect your testosterone levels? A study published in the Nutrition Journal suggests that it may help prolong testosterone’s effects by slowing down how fast the body metabolizes it.

Testosterone is broken down in the liver by a process known as glucuronide conjugation. The enzyme involved in this process is called UGT2B17, and belongs to the UDP-glucuronosyltransferase (UGT) enzyme family. Certain medications—such as non-steroidal anti-inflammatory drugs (NSAIDS) which include ibuprofen and naproxen—and flavonoids (catechins in certain teas) have been shown to inhibit UGT2B17 when used with testosterone, thus increasing the availability of testosterone in the body.

A British study evaluated the inhibitory nature of the common phenolic components found in wine on the activity of the UGT2B17 enzyme. In a laboratory setting, Carl Jenkinson, et al. measured initial testosterone levels and then added evaporated red wine at concentrations varying from 2-8%. The study’s aim was to determine the extent to which wine inhibited the UGT2B17 enzyme in the body.

One and two hours after the addition of the red wine, Jenkinson, et al. analyzed the remaining testosterone to determine if there was any increase in testosterone concentration. The results from this portion of the testing showed glucuronidation through the UGT2B17 enzyme was reduced to 10-70% of normal activity levels. The highest level of reduction was seen after measuring testosterone levels two hours after adding 8% red wine.

The main phenolic components of red wine were found to be gallic acid, chlorogenic acid, caffeic acid, and quercetin. The reduction of glucuronidation of testosterone by the UGT2B17 enzyme was statistically significant for quercetin and caffeic acid, which reduced glucuronidation activity by 28.01% and 78.9%, respectively.

Even though these results were statistically significant, it is difficult to know if they are clinically significant because we do not know to what extent testosterone concentrations were altered. The results are promising, showing that testosterone metabolism was reduced by a wide margin from what is normally seen. Perhaps one day practitioners may recommend a glass of wine with a patient’s testosterone supplement, or (more likely) a quercetin supplement, which could lead to better testosterone availability for patients.

Jenkinson C, Petroczi A, Naughton DP. Red wine and component flavonoids inhibit UGT2B17 in vitro. Nutr J 2012; 11:67. doi: 10.1186/1475-2891-11-67.

Could Red Wine Prolong the Effects of Testosterone?2018-12-21T14:42:07-05:00

Sarcopenia: Age-Related Muscle Loss

Sarcopenia: Age-Related Muscle Loss

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

woman lifting weightsSarcopenia, the muscle loss related to aging, may start slowly in your thirties and continue progressing with growing rapidity into your seventies. It is not identified with definite biomarkers as medical practitioners prefer to use today. Sarcopenia tends to get an “I know it when I see it” sort of diagnosis.

Although this difficulty in diagnosing sarcopenia is understandable considering the mental picture of the frailty associated with aging, loss of muscle mass is a major health issue.

  • With a loss of muscle comes a loss of strength
  • It is more difficult to get around, climb stairs, or walk long distances
  • It leads to falls and serious injuries including broken bones
  • When injuries occur, it takes longer to heal
  • Surgeries may be less successful and infections take hold more readily

Unless measures are taken to stop it, sarcopenia may lead to prolonged hospitalizations, nursing homes, and possibly even death.

Anabolism and Catabolism

Our bodies are in the constant process of remodeling. We build and rebuild molecules, break down old cells and tissues to make way for the new, and dispose of or reuse the molecules. When we are young the rate at which we rebuild (anabolism) exceeds the rate at which we break down (catabolism). There are multiple factors that trigger more catabolism than anabolism as we age, including:

  • Changes in neurochemistry
  • Hormone imbalances
  • Production of inflammatory cytokine (cells produced by the immune system that act on other cells)
  • Inadequate nutrition
  • Environmental hazards
  • Declining physical activity

Satellite Cells

Muscle is composed of many different cell types. Muscle stem cells are called satellite cells. Satellite cells are located on the outside membrane of the muscle cells and next to the blood vessels. These cells are not active unless there is some stimulus from injury to the muscle or from the environment carried in the blood stream. When activated, these satellite cells become new muscle cells.

Estradiol and Testosterone

Sarcopenia develops with the decline of sex hormones. Research in the last decade reveals that the satellite cells have receptors for–and respond to—estrogens (such as estradiol) and androgens (such as testosterone). Studies support that estradiol has beneficial effects on muscle strength.

Most muscle cell types have receptors for testosterone, but testosterone receptors predominate in satellite cells. Administration of testosterone increases the number of satellite cells, and also directly inhibits inflammatory cytokines. Higher testosterone levels contribute to increased strength and mass; since women generally have less testosterone than men, this might explain why women tend to develop sarcopenia at twice the rate as men. 

DHEA and Human Growth Hormone

Adrenal DHEA, another androgen, also declines with age, and may affect muscle strength via a number of mechanisms.  DHEA is converted to estrogens and testosterone in the body, which may have a direct effect on receptors. Also, DHEA increases sensitivity to insulin, another anabolic hormone, which may also increase levels of IGF-1 (the active metabolite of growth hormone). Increased IGF-1 may indicate increased levels of growth hormone. Growth hormone has been shown to increase muscle mass in many studies.

The Triad of Frailty

In their article Frailty and the Older Man, Drs. Jeremy Walston and Linda Fried proposed looking at the concept of frailty in the elderly as a triad:

  1. With aging the hypothalamic responses to stress change, cortisol levels increase, and the signals to produce sex hormones and growth hormone decline
  2. The immune system is affected, producing fewer antibodies and more inflammatory cytokines
  3. Both of these effects contribute to sarcopenia

All three systems are interdependent: the endocrine system, the immune system, and the muscular system participate together in a spiral of decline.

Conclusion

Maintaining the health of the body requires collaboration between various factors. Our awareness of these factors gives us the tools to optimize our aging with strong bodies. Such factors include:

  • Eating well and ensuring our digestive systems work
  • Bolstering our metabolic processes with vitamins and minerals
  • Avoiding environmental challenges to our biochemistry

In addition to these factors, our health is profoundly affected by hormones. Sarcopenia illustrates how hormone deficiencies hinder us from achieving optimal health. Fortunately, our ability to supplement the hormones that decline as we age may help stave off the effects of sarcopenia and other age-related conditions.

A validated questionnaire called FRAIL can be used as a simple screen for sarcopenia. Three or more “Yes” answers are considered “frail,” signalling the possibility of sarcopenia.

  1. F. Fatigue: Did you feel tired all or most of the time in the last 4 weeks?
  2. R. Resistance: Is it difficult to walk up 10 steps without resting?
  3. A. Ambulation: Is it difficult to walk several hundred yards?
  4. I. Illnesses: Do you have more than four illnesses?
  5. L. Loss of weight: Have you lost 5% of your normal weight in the last year?
  • La Colla A, et al. 17 Beta Estradiol and testosterone in sarcopenia: Role of satellite cells. Aging ResRev. 2015 Nov:24(Pt B): 166-177. doi: 10.1016/j.arr.2015.07.011. Epub 2015 Aug 3.
  • Health Sciences Institute. This hidden disease will land you in a nursing home. February 2016 (20) 6.
  • Walston J, Fried L. Frailty and the Older Man. Med Clin North Am. 1999 Sept;83(5):1173-1193.
  • Balagopal P, Proctor D, Nair KS. Sarcopenia and Hormonal Changes. Endocr. (1997) 7:57-60. https://doi.org/10.1007/BF02778064.
  • Morley JE, Malmstrom TK. Frailty, Sarcopenia, and Hormones. Endocrinol Metabl Clin N Am. (2013)42:391-405. https://doi.org/10.1016/j.ecl.2013.02.006.
  • Morley JE, Malstrom TK, Miller DK. A simple frailty questionnaire (FRAIL) predicts outcomes in middle aged African Americans. J Nutr Health Aging. 2012 Jul;16(7):601-8.

© 2018 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

Sarcopenia: Age-Related Muscle Loss2019-02-13T09:53:55-05:00

DHEA and Healing Skin Wounds

DHEA and Healing Skin Wounds

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

DHEA may improve skin's ability to healDehydroepiandrosterone (DHEA) is produced primarily by the adrenal glands and is the most abundant of all the steroidal hormones. The quantity of DHEA in the body drops significantly during the aging process. This is so predictable that DHEA levels could be regarded as an aging biomarker.

One of the problems of aging is that it impairs the rate of wound healing in the skin. Many people begin to notice that cuts take longer to heal as they age. Ulcerations may develop which become chronic.

In the UK, Stuart J. Mills and colleagues at Manchester University investigated the role of DHEA in aging skin. This group had already demonstrated that estrogens have a positive effect on skin healing whether used directly on the wound or throughout the body. They wondered if DHEA would have a similar effect, since it is an immediate precursor of both estrogen and testosterone. Understanding that DHEA has many positive effects on the immune system, the researchers also wanted to establish whether DHEA would work directly, or whether it had to be converted into estrogen or testosterone to be effective in healing skin wounds.

First, they compared two groups of human subjects. Those suffering from ulcerations or other signs of slow wound healing were compared with healthy individuals with normal healing. The researchers were able to demonstrate that those with slow skin healing had significantly lower DHEA levels in their blood than the healthy group.

Next, they procured estrogen-deficient mice. Unlike humans, mice do not produce DHEA but they do have the necessary enzymes in their skin to convert DHEA to estrogen or testosterone. After producing superficial wounds, the researchers gave these mice DHEA throughout their bodies. This did not produce any noticeable effect on healing. However, a marked increase in healing did occur when DHEA was applied directly to the damaged skin area.

Finally, in order to determine whether DHEA was working directly or whether the metabolites of estrogen or testosterone were the key to improved healing, the researchers used substances that blocked the conversion enzymes for estrogen and testosterone. Healing and inflammation relief did not occur when estrogen production was blocked. With only testosterone blocked, however, the benefits of the DHEA treatments remained. Mills et al. concluded that DHEA could be effective for targeted treatment of damaged skin, and that the effectiveness depended on the conversion to estrogen and its local action on estrogen receptors.

  • Mills SJ, et al. The Sex Steroid Precursor DHEA Accelerates Cutaneous Wound Healing Via the Estrogen Receptors. J Invest Dermatol. 125: 1053-1062 2005.

© 2018 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

DHEA and Healing Skin Wounds2018-11-05T13:27:54-05:00

Book Review – The End of Alzheimer’s

Book Review – The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline by Dale E. Bredesen, MD.

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

older couple taking a walkAlzheimer’s disease is a grim disease that causes both the mind and body to deteriorate. In 1906, Dr. Aloysius Alzheimer identified plaques in the brain autopsy of a patient who had suffered from dementia, and in doing so he discovered what is generally thought to cause the symptoms of the disease that bears his name. These plaques, made from a protein called amyloid-beta, are thought to interfere with the functioning of our brains.

Since Dr. Alzheimer’s discovery over a century ago, the focus has not been in pinpointing the cause of Alzheimer’s disease, but rather in finding an effective treatment for the related symptoms. Theoretically, if we can find a drug that will stop the formation or contribute to the removal of plaques in the brain, we will be able to prevent or reverse the development of the symptoms associated with Alzheimer’s disease. We have been using this line of thinking to develop drugs since the 1980s, without success.

Dr. Dale Bredesen has turned this thinking upside down. His book, The End of Alzheimer’s, poses the questions: What if the amyloid proteins are there to protect the brain rather than disrupt the brain? Is it only when plaque formation is excessive that it interferes with nervous tissue signaling?

A Leaky Roof

Dr. Bredesen uses the metaphor of a leaky roof for Alzheimer’s disease. The roof has approximately 36 “holes,” though a few more may yet be identified. These holes signify the number of contributors he and his team have identified as playing a role in the development of dementia and Alzheimer’s disease.

The size of the holes—that is, the probability of developing Alzheimer’s disease–depends on the impact of genetics and the environment. Because each hole is a different size (depending on genetics and other factors) for each person, not every single hole needs to be patched; however, if you only patch one hole in the roof, you will still have a leaky roof. Our pharmaceutical model only has touched on one pathway—trying to stop the formation of plaques—and overlooked other possible causes, which is why our attempts at treating Alzheimer’s disease have failed.

What Causes Amyloid Production?

Among the 36 “holes” that contribute to developing Alzheimer’s disease, there are three major categories. These categories contain conditions that can be grouped together. The three major categories are inflammation, deficiencies in hormones or nutrients, and exposure to stress or environmental toxins. All of these conditions force the body to defend the brain by producing amyloid plaques, thus leading to Alzheimer’s disease.

Inflammation is the first category that may increase amyloid production. While inflammation is often related to infection, it may be caused by other things such as food or food sensitivities. Dr. Bredesen uses the example of ingesting trans-fats or sugar, substances that are known to be inflammatory.

The second category includes hormones and nutrient deficiencies and imbalances that interfere with neuronal repair in the brain. For example, vitamin D deficiency may be a critical trigger for amyloid production. See below for a more detailed description of this category.

The third category includes exposure to significant stress, poisoning with heavy metals and mold toxins, or other environmental or chemical exposures. Even the stress of menopause may instigate the disease. Because this category tends to present psychological symptoms (such as depression), which mask the symptoms of Alzheimer’s disease, these contributors can be easily missed.

Alzheimer’s Disease By the Numbers

The Alzheimer’s Association has gathered these statistics about this increasingly-prevalent disease:

  • An estimated one in ten of people over the age of 65 is affected.
  • Two-thirds of those diagnosed are women.
  • It is the sixth leading cause of death in the United States.
  • Life expectancy after diagnosis is 4 to 8 years.
  • The cost of care for Alzheimer’s disease and other dementias in the United States is estimated at $277 billion for 2018 alone.
  • One-third of seniors die with Alzheimer’s disease or another form of dementia.
  • 7 million Americans are living with dementia as of 2018.
  • In the United States, every 65 seconds a patient is diagnosed with Alzheimer’s disease.

Hormones Are a Key

As mentioned above, some of Dr. Bredesen’s findings show that the key to preventing or recovering from Alzheimer’s disease may be restoring depleted hormone levels. Of the 36 and more contributors identified, several involve hormonal imbalance. Dr. Bredesen states, “Reaching optimal hormone levels is one of the most effective and most critical parts of ReCODE (reversing cognitive decline protocol).” Based on his observations, Dr. Bredesen recommends optimizing:

  • Insulin secretion and signaling
  • Estradiol
  • Progesterone
  • The ratio of progesterone to estradiol
  • Free T3 (the active thyroid hormone liothyronine)
  • Free T4 (the thyroid hormone thyroxine which is the precursor to T3)
  • Thyroid stimulating hormone (TSH), made by the pituitary gland to stimulate the thyroid gland to produce T3 and T4
  • Pregnenolone
  • Testosterone
  • Cortisol
  • Dehydroepiandrosterone (DHEA)

Dr. Bredesen takes great care to explain the development of his ideas and the work in his laboratory. With decades of research behind him, he presents a theory addressing everything we do know about Alzheimer’s disease, and as a researcher and physician, he has been able to practically apply this theory to successfully treat patients.

Connection with Insulin

Another contributor to inflammation—and by extension, developing Alzheimer’s disease—is insulin resistance. Insulin resistance, metabolic syndrome, and diabetes all involve abnormally high levels of insulin. Some even call Alzheimer’s disease “Type 3 diabetes” because of the problems high insulin levels cause the brain. Dr. Bredesen explains that the enzyme, insulin degrading enzyme (IDE), helps us break down excessive insulin. This same enzyme can break down amyloid. If we follow a lifestyle and eating program that constantly elevates insulin, IDE may not be available in amounts needed to break down and help stop amyloid overproduction.

Sex, Adrenal, and Thyroid Hormones

A common factor of aging is the depletion of adrenal hormones (although cortisol is sometimes high), sex hormones, and thyroid hormones. The loss of hormones parallels an increased risk of Alzheimer’s disease as we age.

For each of the markers that Dr. Bredesen has identified, he also describes how to test or evaluate hormone levels, and presents what he believes are the optimal parameters. Replenishing these depleted hormones may help patients prevent or recover from Alzheimer’s disease. To restore proper hormone function, bioidentical rather than synthetic hormone replacement must be used, as bioidentical hormones are equivalent in structure to the hormones our own bodies make.

Diagnosing Alzheimer's Disease

Alzheimer’s disease used to be diagnosed only after the patient had died. An autopsy would reveal the presence of amyloid plaques, explaining the decline in the patient’s health and eventual death. Now we have testing that can identify the presence of plaques during the patient’s own lifetime. These include scans of the retina, brain scans, and checking the cerebral spinal fluid. A genetic test for Apolipoprotein (APO)E also shows potential to predict susceptibility to this disease.

Mending the Holes in the Roof

Alzheimer’s disease does not follow the “one disease, one treatment” model our current medical system relies upon. Each patient should be evaluated for their individual needs. Successfully treating Alzheimer’s must involve a personalized, complex therapy program, but the reward—giving patients the ability to reclaim their brains and their lives—makes the effort more than worthwhile. The End of Alzheimer’s presents an opportunity to forestall and correct the onslaught of this devastating disease. Thanks to his groundbreaking work, dedication to making this information available, and training practitioners to use his guidelines, Dr. Bredesen demonstrates that patients with Alzheimer’s disease do have treatment options.

© 2018 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 – The End of Alzheimer’s2018-10-08T10:45:16-05:00

Virility Drugs for Erectile Dysfunction…What about Sex Hormones?

Virility Drugs for Erectile Dysfunction…What about Sex Hormones?

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

Virility drugs such as Viagra, Cialis and Levitra work by inhibiting the breakdown of cyclic guanosine monophosphate (cGMP), a molecule which enables the penis to fill with blood and become erect for intercourse. However, these treatments are not always a “magic bullet.” They may not work for many men who try them and they may not enable the same quality of erections men experience in their teenage years.  Also, they do not increase sexual desire and using these drugs does not address any of the underlying medical conditions that may be the cause of erectile dysfunction (ED).

The linchpin in the series of reactions needed for healthy erections is cGMP. The enzyme PDE5 acts to break down cGMP. Virility drugs block the PDE5 enzyme which prolongs cGMP activity in the penis allowing it to fill with blood and become erect. Although these drugs can restore erectile function by slowing the enzymatic breakdown of cGMP, hormones, such as estrogens, progesterone, androgens (e.g., DHEA, testosterone and dihydrotestosterone (DHT)), insulin, and growth hormone can actually increase cGMP production by modulating nitric oxide (NO) production.

NO is an extremely important signaling molecule generated in the body and lasting just a few seconds before it is broken down. It is a potent smooth muscle relaxant and mediates the transformation of guanosine triphosphate (GTP) into cGMP. Hormones are important modulators of NO production and stimulate the production of NO and cGMP. By contrast, glucocorticoids (for instance, cortisol) and prolactin can reduce the bioavailability of NO, possibly reducing the amount of available cGMP as well.

Documentation submitted for a US Patent by Steven Ferguson reveals interesting observations and data about ED. The patent application centers on a clinical trial of 20 men with ED, ranging in age from 21 to 88 years old.

When measuring their hormone status, Ferguson found that these men were low in testosterone, low in progesterone, and normal to high in estradiol. All had some health issue(s) such as hypertension, diabetes, heart disorders, prostatic hyperplasia, renal insufficiency, depression, high cholesterol, chronic obstructive pulmonary disease (COPD), or cerebral palsy. Many of these health issues or the drug treatments for them are known as risk factors for the development of ED. Ferguson’s treatment was to supply progesterone and testosterone together in topical creams which were applied to non-hairy skin areas daily.

Ferguson’s group was reflective of the general health status of men who experience erectile dysfunction. In one to three months, the majority of men treated with his progesterone with testosterone cream were able to achieve full erections. These results were stunning in that no attempt was made to address any underlying disease states.

Although virility drugs are widely used, they do not address the underlying cause of ED. Diminished hormone production with aging or from other causes may be the root of the problem. Ferguson’s successes illustrate just how important hormone balance can be in reversing ED.

  • Duckles S, Miller V. Hormonal Modulation of endothelial NO production. Pflugers Arch. 2010 May; 459(6): 841–851
  • Ferguson SW. Progesterone/testosterone cream for erectile dysfunction. Google Patents. https://www.google.com/patents/US20070167418. September 7, 2004. Accessed July 2018.
  • Huang SA, Lie J. Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P T. 2013 Jul; 38(7): 407, 414-419. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776492/. Accessed July 2018.

© 2018 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

Virility Drugs for Erectile Dysfunction…What about Sex Hormones?2018-09-11T14:42:30-05:00

Metallo-estrogens

Metalloestrogens

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

gears with rustThe world abounds with substances that affect hormone balance. It is widely accepted that that there are many organic substances that affect hormone activity in the body. For example, soy has estrogen-like qualities and ginseng acts as an adrenal adaptogen. We can use these organic substances in ways that are beneficial to the body. On the other hand, organic substances like phthalates, PCBs and BPA mimic estrogens in a negative way. They create a burden of too much estrogen activity in the body.

Researchers are now turning to inorganic sources of hormone disruption. In 2006, Dr. Philippa Darbre published a paper that identified many metals that have an effect on estrogen receptors. These effects include: altering gene expression, estrogenic activity, and displacing estrogens from estrogen receptors. Metals that have been identified to exert an influence on estrogen receptors include aluminum, antimony, arsenite, barium, cadmium, chromium, cobalt, copper, lead, mercury, nickel, selenite, tin, and vanadate. These metals are referred to as metalloestrogens. The paper also identified metalloestrogen activity at progesterone, testosterone and glucocorticoid (hydrocortisone-like) receptors. For example, cadmium has been shown to produce testosterone activity, displace testosterone from testosterone receptors and affect gene changes. Dr. Darbre concludes that all steroid hormone receptors may be affected.

Some metalloestrogens are essential minerals. Cobalt, chromium, copper, and nickel are all needed in trace amounts for normal human body function. When the amounts of these minerals exceed the amount needed by the body, they begin to interfere with the hormone receptors.

Other metalloestrogens, such as cadmium, aluminum, and lead, are not needed by the body in any amount. Cadmium is problematic because the human body doesn’t have an enzyme system to eliminate it once we are exposed. Making matters worse, the kidneys reabsorb cadmium rather than eliminate it. The amount of cadmium in our bodies continues to increase as we age. Common sources of cadmium, outside of industrial uses, include cigarette smoke and certain foods due to cadmium pollution in our environment. Cadmium may be a trigger for endometriosis. Several studies point to an association between the presence of cadmium in the body and endometrial tissue proliferation. One especially interesting study found melatonin was able to block the estrogenic effect of cadmium in endometrial tissue.

Lead acts as a metalloestrogen by occupying hormone receptors. Unsurprisingly, lead contributes to a number of health conditions. The Environmental Protection Agency (EPA) recognizes lead can cause a number of problems for women. After menopause, increased levels of lead in the body increase one’s risk for hypertension, atherosclerosis, reduced kidney function, and decreased cognitive functioning with symptoms similar to dementia. Osteoporosis, another condition common in menopause, can cause lead to be released into the body as bone breaks down. Those of us who have been exposed to lead paints and leaded gasoline have higher levels of lead in our bones, causing higher levels of lead in our bodies as lead is released from our bones. (For more information, read our article Lead Toxicity and Disease.)

As research expands and we dig deeper into hormone balance issues, more information emerges to help us solve the riddle of hormone imbalance. The effects of metalloestrogens are not always considered by busy practitioners. Furthermore, many are not trained to help reduce the body’s load of metalloestrogens. Three medical groups that focus on reducing metalloestrogens in the body are the International College of Integrated Medicine (www.icimed.com), the American College for Advancement in Medicine (www.acam.org), and the American Association of Naturopathic Physicians (www.naturopathic.org).

  • Darbre PD. Metalloestrogens: An Emerging Class of Inorganic Xenoestrogens With Potential to Add to the Oestrogenic Burden of the Human Breast. J Appl Toxicol. 2006 May-Jun;26(3):191-7. DOI:10.1002/jat.1135.
  • U.S. Environmental Protection Agency Aging and Sustainability List Serve
  • Silva N, et al.  Metalloestrogen cadmium stimulates proliferation of stromal cells derived from the eutopic endometrium of women with endometriosis.Taiwan J Obstet Gynecol. 2013 Dec;52(4):540-5.
  • Jackson LW, Zullo MD, Goldberg JM. The association between heavy metals, endometriosis and uterine myomas among premenopausal women: National Health and Nutrition Examination Survey 1999 – 2002. Hum Reprod. 2008 Mar;23(3):679-87. DOI: 10.1093/humrep/dem394. Epub 2008 Jan 12.
  • Chemical of the Day. Metalloestrogens. https://chemicaloftheday.squarespace.com/most-controversial/2014/9/4/metalloestrogens.html. September 2014. Accessed August 2018.
  • Martínez-Campa C, et al. Melatonin inhibits both ER alpha activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium. J Pineal Res. 2006 May;40(4):291-6.
Metallo-estrogens2018-09-12T10:29:02-05:00

Premature Balding in Men

Premature Balding in Men

A Symptom of Metabolic Syndrome and Benign Prostatic Hyperplasia

Written by Women’s International Pharmacy Staff

premature balding in menAccording to Statistic Brain, 35 million men in the US experience hair loss, 40% of which have hair loss by the age of 35.(i) The same hormonal imbalances that contribute to early onset balding may also cause more serious conditions. Because of its strong association with hormone imbalances, prostate enlargement, and metabolic syndrome, premature hair loss could be indicator for men of deeper health concerns.

A Male Version of PCOS?

Polycystic Ovary Syndrome (PCOS) is a hormonal disorder common among women of reproductive age. At the Progressive Medical Education meeting in Irvine, CA in August 2017,(ii) Dr. Matthew Cavaiola presented a hypothesis published by Kurzrock et al.(iii) He stated because the primary defect underlying PCOS may not be a defect in the ovaries themselves, it is possible that this condition can also occur in men.

Symptoms of PCOS in women include:

  • High androgen hormones (like DHEA and testosterone) in the blood
  • Obesity focused on the waistline
  • High insulin levels
  • Development of diabetes
  • Infertility

Dr. Cavaiola stated that young men can suffer from similar symptoms:

  • Insulin resistance
  • Obesity
  • Increased risk for diabetes and cardiovascular disease
  • Early onset of male pattern baldness
  • Excessive body hair
  • High levels of testosterone and dihydrotestosterone (DHT, the active form of testosterone)

In addition to the symptoms listed above, sex hormone binding globulin (SHBG) levels may be low which further increases the amount of available testosterone and DHT in the body. Dr. Cavaiola also pointed out that when SHBG levels are low, insulin levels are abnormally high. Persistently high levels of insulin may lead to metabolic syndrome, prediabetes, and diabetes.

Prostate Enlargement and Insulin Resistance

Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is the enlargement of the prostate gland and is a common condition as men age. Common signs and symptoms of BPH include a frequent or urgent need to urinate, increased frequency of urination at night (nocturia), difficulty starting urination, a weak urine stream or a stream that stops and starts, dribbling at the end of urination and an inability to completely empty the bladder. There appears to be a strong correlation with early onset balding and BPH, as men with BPH tend to have more inherited baldness and an increased severity of baldness. Some studies also point to an increased risk of prostate cancer.(iv, v)

Insulin Resistance

Insulin is a hormone made by the pancreas. It allows cells in the body to use glucose (sugar) for energy. Insulin resistance (also called metabolic syndrome or prediabetes) is a condition where cells throughout the body don’t recognize insulin as they should. This causes the cells to have trouble absorbing glucose, which causes a buildup of sugar in the blood. It also causes the body to produce more insulin leading to high insulin levels in the body. These high levels of insulin may be a major contributor to BPH and early onset balding as postulated by Ajit Vikram et al.(vi)

Insulin resistance may also be associated with, high blood pressure, high triglycerides and acanthosis nigricans (dark patches of skin usually on the back of the neck, groin, and armpits).

Treatment Options

Addressing Baldness and Prostate Enlargement with Finasteride

Drug companies have come up with a possible solution for hair loss and prostate hyperplasia with a synthetic molecule, finasteride. Finasteride is the generic name for two prescription drugs: Propecia and Proscar. Propecia has been approved by the FDA to treat male pattern baldness at a dose of 1 mg per day. Proscar is the same drug in a 5 mg dose, and has been approved to treat BPH. Finasteride inhibits the 5 alpha reductase enzyme, which is the enzyme responsible for converting testosterone into its more active form, (DHT). Studies suggest high levels of DHT may be responsible both for male pattern baldness and BPH.

Negative Side Effects of Finasteride

There are a number of negative side effects that have been associated with finasteride. The Post Finasteride Syndrome Foundation studies these persistent adverse effects,(vii) which include:

  • Loss of penis sensitivity
  • Decreased ejaculatory force and volume
  • Loss of libido and low penile temperature
  • Reduced feeling of pleasure or emotions
  • Lack of mental concentration
  • Loss of muscle tone/mass
  • Severe depression, suicidal ideation, and suicide
Why Not Progesterone?

Progesterone, a hormone that naturally occurs in the human body, also acts as a 5 alpha reductase inhibitor,(viii) as well as having a great number of other important functions in the body. The drug, finasteride, structurally resembles progesterone. The prostate has receptors for progesterone in addition to receptors for androgens (testosterone and derivatives) and estrogens. While many studies have explored the relationship of prostate enlargement and prostate cancer to androgen and estrogen receptors, little research exists for the relationship to progesterone.

Progesterone is produced in men by the testes and the adrenal glands. Men have progesterone levels similar to a woman’s progesterone levels during the follicular phase of the menstrual cycle. RuiQi Chen et al. present a case for inhibition of prostate enlargement—and possibly prostate cancer—using progesterone.(ix)

Conclusion

Some men may consult a practitioner when confronting hair loss and may be prescribed Propecia in an attempt to grow hair back, but why use a synthetic drug when rebalancing hormone levels with progesterone, a hormone natural to the body, may help? Hair loss may be the first sign of hormone imbalances that could lead to metabolic syndrome and prostate hyperplasia. Other potential risks may include high blood pressure, high cholesterol, obesity, diabetes, and heart disease. By proactively considering hormone balancing solutions, men may forestall the loss of their hair and prevent more drastic declines in their health.

  • (i) Statistic Brain. Hair Loss Statistics. https://www.statisticbrain.com/hair-loss-statistics/. August 2016.
  • (ii) Cavaiola M. Environmental Medicine: Focus on Men’s Health & Longevity. A presentation at the Progressive Medical Education Meeting. August 2017.
  • (iii) Kurzrock R, Cohen PR. Polycystic ovary syndrome in men: Stein-Leventhal syndrome revisited. Med Hypotheses. 2007;68(3):480-3. Epub 2006 Nov 28. (3)
  • (iv) Oh BR, et al. Association of benign prostatic hyperplasia with male pattern baldness. Urology. 1998 May;51(5):744-8.
  • (v) Papa NP, et al. Early onset baldness and the risk of aggressive prostate cancer: findings from a case-control study. Cancer Causes Control. 2018 Jan;29(1):93-102. doi: 10.1007/s10552-017-0981-0. Epub 2017 Nov 14.
  • (vi) Vikram A, et al. “Insulin-resistance and benign prostatic hyperplasia: The Connection” Eur J Pharmacol. 2010 Sep 1;641(2-3):75-81. doi: 10.1016/j.ejphar.2010.05.042. Epub 2010 Jun 9.
  • (vii) Post-Finasteride Syndrome Foundation. https://www.pfsfoundation.org. Last accessed: April 2018.
  • (viii) Ling YZ, et al. Synthesis and in vitro activity of some epimeric 20 alpha-hydroxy, 20-oxime and aziridine, pregnene derivatives as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase and 5 alpha-reductase. Bioorg Med Chem 1998;6:1683-1693. https://www.ncbi.nlm.nih.gov/pubmed/9839000
  • (ix) Chen R, et al. Progesterone receptor in the prostate: A potential suppressor for benign prostatic hyperplasia and prostate cancer. J Steroid Biochem Mol Biol. 2017 Feb;166:91-96. doi: 10.1016/j.jsbmb.2016.04.008. Epub 2016 Apr 25.
  • Fung J. The Obesity Code: Unlocking the Secrets of Weight Loss. Greystone Books; Vancouver, BC, Canada: 2016.
Premature Balding in Men2018-07-17T16:31:21-05:00