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

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

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

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

A New Organ Has Been Identified: The Human Microbiome

A New Organ Has Been Identified: The Human Microbiome

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

That’s right. It has been there all along, but we are just now getting around to noticing it. This organ weighs about three pounds and by weight, it is the largest organ in the human body. The organ is a collection of microbes or single celled organisms that live on and in your body. It has been named the human microbiome.

Our bodies are made up of about 10 trillion cells, but we host approximately 100 trillion microbe cells. To put a trillion in perspective, if we were to live for one trillion seconds, our life span would exceed 32,000 years. Based on the math, we are only 10% human!

It was surprising to the scientific community when the Human Genome Project was completely finished earlier than anyone predicted. It turns out that human beings only have about 20,000 genes. We have significantly fewer genes than rice or corn! However, we also carry and use two to twenty million genes from the vast number of microbes we host. If we compare the number of human genes to microbe genes rather than the number of human to microbe cells in our body, we are 99% microbe!

In an effort to identify the microbes living on and in the human body, the Human Microbiome Project was begun in 2008. It was a massive undertaking funded by the National Institute of Health (NIH) to the tune of 170 million dollars. More than 200 scientists worked on the project. The Human Microbiome Project continues to generate significant scientific findings to this day. Some examples include new technologies that sequence genes and computer programs which can handle vast amounts of data. These discoveries are opening up very exciting new areas of research.

Our human microbiome makes us more individually unique than our genetic composition. Genetically we are 99% identical to other human beings, but we only share about 10% with other human microbiomes. Even genetically identical twins do not share the same microbiome.

Since the time of Louis Pasteur, we have been operating on the “germ theory of disease.” This philosophy states that diseases are caused by microorganisms. One might assume that we are hapless victims of microbial assaults and to save ourselves we must use antiseptics or antibiotics to stem the attack. The latest findings of the Human Microbiome Project cause one to think twice about this assumption.

Normally, we live in harmony with these vast numbers of microbes. In fact, a healthy microbiome aids us in some essential life processes such as digestion, the integrity of our immune systems and even our behavior. However, many different things can cause changes in the composition of an individual’s microbiome. Diet, drugs, birth order, age, sexual partners and especially antibiotics are just a few examples. An altered or weakened human microbiome has been linked to diseases such as obesity, arthritis, autism, and depression.

The human microbiome also plays a role in hormone production and regulation in the body. For example, an organism called Clostridium scindens, which resides in the gastrointestinal tract, has been identified as capable of transforming cortisol type hormones to testosterone and other androgens. Surprisingly, our sex glands are not the only source of testosterone in our bodies! The genes of some bacteria in the gut are able to produce estrobolome, an enzyme which helps metabolize estrogens. A disordered microbiome in the digestive tract could be the underlying cause of estrogen dominance producing symptoms of infertility, PMS, heavy bleeding, cramps, polycystic ovary disease and more

Additionally, an overgrowth of yeast and related organisms in the microbiome has many documented effects on various hormones. Request a yeast information packet which contains a detailed chart of specific organisms and their impact on hormone balance.

Since so many different things can alter the microbiome, research is focusing on how to repair a damaged microbiome system. For example, scientists have found altering the microbiome normalizes the weight of obese mice. We have also seen amazing results with procedures called fecal transfers where the microbiome of a healthy person is essentially implanted into the body of a sick person.

We have long been using probiotics in the forms of specific cultures or in fermented foods. We also know about the use of substances which we call prebiotics such as inulin or fructo-oligosaccharides (FOS) that can nurture the growth of certain species of microbes. We are just now beginning to understand which species of microbes need to be re-established and how to reintroduce these specific strains with supplementation. For the consumer, the marketplace for probiotics can be confusing and frustrating. There may be very helpful probiotic strains available, but we still lack the knowledge of which probiotic strain we should choose for each particular condition.

While the science is still evolving, there is a lot we can do in the meantime. We can avoid the frivolous use of antibiotics and avoid eating antibiotic treated meats. We can carefully consider the need for certain medication before using them. Drugs like oral contraceptives may damage the microbiome. We can clean up our diet and avoid dairy, sugar and gluten which can adversely affect the microbiome. We can eat fermented foods like sauerkraut, kimchi, kombucha, and live culture yogurt daily. We can add probiotics and prebiotics to our daily regimen. Because the science has not caught up yet, try a variety of products to determine which might have the best effect for you. We are clearly entering an exciting new world of understanding how we, as human beings, interact with the invisible yet powerful world of microbes.

A New Organ Has Been Identified: The Human Microbiome2018-04-03T16:31:26-05:00

Book Review – Venus on Fire, Mars on Ice

Book Review – Venus on Fire, Mars on Ice: Hormonal Balance – The Key to Life, Love and Energy by John Gray, PhD

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

In his book Men are From Mars, Women are From Venus, Dr. John Gray focused on the differences between men and women; in Venus on Fire, Mars on Ice he delves into why those differences occur. Dr. Gray explains that, not only do we need a balance of hormones for managing PMS, post-partum depression, menopause, and andropause, but hormone balance also has a great impact on our relationships. Specifically, coping mechanisms for stress affect our relationships, and hormones play a vital role in the different ways men and women use to deal with stress.

Cortisol

Due to unrelenting demands of life in the modern world, many men and women are constantly stressed. As a result, cortisol production–which is designed to reach peak levels when challenged with an emergency and then quickly drop down–stays at a high level. A chronic high level of cortisol may contribute to emotional instability (among other things), which can affect relationships.

When trying to reduce or deal with stress, men release testosterone and women release the pituitary hormone oxytocin. High cortisol levels may interfere with normal production of both testosterone and oxytocin, hampering both men and women from their attempts at stress reduction.

Testosterone and Oxytocin

When a man’s testosterone level is adequate, it allows him to react in urgent situations where he needs to focus keenly, step up, and solve a problem. In fact, solving problems may cause some men’s testosterone levels to actually rise, while simultaneously lowering stress hormones like cortisol.

While small amounts of testosterone will also help women feel good, too much will actually increase their stress levels. Higher testosterone levels in women might be useful for competition, such as in the workplace, but sustained high levels of testosterone take a toll. When women get home from work, their stress levels may rise as they face the pressures of all the things that need to be done.

In contrast with the use of procrastination to increase testosterone in men, planning ahead stimulates oxytocin release in women. For women, a release of oxytocin makes them feel safe and nurturing, feelings that in turn encourage oxytocin levels to rise further. On the other hand, oxytocin doesn’t help men deal with stress and can even bring their testosterone levels down.

Insulin and Serotonin

Other fundamental substances that play an important role in relationships include the hormones insulin and serotonin and their interaction with glucose (blood sugar). Every cell in the body needs a consistent supply of glucose to function, and insulin controls how it is utilized. The brain is particularly sensitive to fluctuations in blood sugar, altering our moods, decision-making abilities, and other aspects of behavior that can affect interpersonal relationships.

When blood sugar drops, the production of serotonin (which has a calming effect) also drops. To make matters worse, the body responds to the low serotonin levels by producing more cortisol, which increases anxiety.

Conclusion

Dr. Gray believes that understanding these basic hormonal differences in each other is the key to maintaining loving relationships. Aging leads to lower levels of testosterone and oxytocin, as well as increased insulin resistance and low serotonin levels. This creates even more difficulty in dealing with stress, and makes hormonal balance even more critical. Dr. Gray suggests that diet and lifestyle are important building blocks to producing and maintaining these hormones in proper balance.

Book Review – Venus on Fire, Mars on Ice2018-07-10T17:41:01-05:00

Can Testosterone Protect Against Breast Cancer?

Can Testosterone Protect Against Breast Cancer?

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

 

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

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

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

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

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

Testosterone in Women

Testosterone in Women – A Commentary

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

 

Professor Susan Davis is a women’s health researcher. In 2005 she became the inaugural Chair of Women’s Health in the Monash University Department of Medicine at the Alfred Hospital in Melbourne, Australia. In addition, she is a consultant endocrinologist at Alfred Health and Cabrini Medical Centre, also in Melbourne.

Professor Davis has been involved in the study of the role of estrogens and androgens (e.g., testosterone and DHEA) in women. She has been investigating the effects of hormones throughout the body, rather than just how they affect reproductive functions. She has published over 300 peer-reviewed articles. She is indeed a giant in the world of research involving the use of testosterone in women.

In December of 1999, Dr. Davis published a commentary on the nature of testosterone replenishment in women. Almost 20 years has passed since this commentary was published, yet not much seems to have changed. Scientists and physicians are still unclear on what actually constitutes a deficiency of testosterone in women. The clinical picture of a woman with adequate testosterone has not been established or agreed upon. There is no agreement on how low testosterone levels must be before action is taken.

The following is a brief synopsis of a number of subjects taken from Dr. Davis’s commentary.

Declining Testosterone

It is well established that testosterone and DHEA production steadily declines with aging. There are also a number other reasons testosterone levels may be low:

  • 50% of testosterone production is lost when the ovaries are removed (oophorectomy) as part of a “complete hysterectomy.”
  • Chemical damage to the ovaries produced by chemotherapy in cancer treatments.
  • The use of estrogen only hormone therapies and oral contraceptives. Both increase sex hormone binding globulin (SHBG), which binds testosterone and prevents the body from using it.
  • Treatment with corticosteroid drugs like prednisone turns off the production of adrenal testosterone. This may be the cause of osteoporosis when using these drugs. It has been established that the best bone mineral density levels are associated with strong levels of testosterone and DHEA.
  • Premature ovarian failure.
  • Loss of cycling due to lost signaling from the hypothalamus.

Sexuality

It has been established that adequate testosterone levels are associated with sexual interest in a way that estrogen levels are not. However, because sexuality is complicated and multi-faceted, using libido and sexual activity as distinct markers for adequate testosterone levels is not reliable. One should also consider vaginal atrophy, pain during intercourse (dyspareunia), loss of interest in a partner, or other psychological factors as contributors to sexual dysfunction.

Bone Loss

Bone loss may continue to occur even with estrogen and progesterone supplementation. When testosterone supplementation is added, bone growth may be restored. Some suggest that testosterone acts as a prohormone for estrogens and that this interplay must be in effect for good bone health.

Body composition

In general, muscle mass declines in the elderly and fat mass increases. Testosterone has been demonstrated to improve muscle mass in postmenopausal women. Additionally, testosterone has been effective in restoring muscle mass in both immune compromised men and women.

Autoimmune disease

Women are more prone to autoimmune diseases. It has been theorized that the higher testosterone levels enjoyed by men contribute to this gender difference. Testosterone replacement has been used successfully in diseases such as autoimmune rheumatoid arthritis.

Premenstrual Syndrome (PMS)

Below average levels of circulating testosterone have been identified throughout the entire menstrual cycle in some women who have PMS symptoms. In Australia and the UK, testosterone has been used for treatment of PMS.

Forward to 2015

In 2015, Dr. Davis published another review article. She added cognition, cardiovascular health, and vaginal integrity, including pain relief to her documentation. She cites numerous studies about the anti-proliferative effect of testosterone in breast and ovarian cancer, but points out it is difficult to draw conclusions without considering the effects of multiple other hormones, including estrogens. In spite of testosterone being a much more prevalent hormone than even estrogen in women, we still don’t know much about its effects. Dr. Davis says that research in women lags about ten years behind where it should be. Too many studies are small and limited in their scope, making solid conclusions impossible.

In Closing

In spite of several attempts to obtain FDA approval for gels and patches delivering testosterone replenishment for women, nothing has been approved. This appears to be due to a lack of consensus on the function of testosterone in women. However, testosterone has been available to women for decades with the assistance of compounding pharmacists. Testosterone can be prescribed in oral capsules, creams, gels, suppositories, drops, troches, pellet implants, and injectables. Thanks to compounding pharmacies, practitioners may choose to treat each of their patients’ testosterone deficiencies and monitor the effects — one patient at a time.

  • Davis SR. Androgen Replacement in Women: A Commentary. J Clin Endocrinol Metab. 1999; 84(6): 1886-91.
  • Davis SR. Testosterone in Women: the Clinical Significance. Lancet Diabetes Endocrinol. 2015 Dec;3(12):980-92. doi: 10.1016/S2213-8587(15)00284-3. Epub 2015 Sep 7.
Testosterone in Women2017-12-14T15:41:59-05:00

A New Treatment Program to Improve Memory Loss

A New Treatment Program to Improve Memory Loss

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

In spite of hundreds of clinical trials over the past ten years, Alzheimer’s disease (AD) has no effective treatment. AD affects 5.4 million Americans, predominately females. It is estimated that women have a greater chance of developing AD than breast cancer.

Research supports the theory that an imbalance in brain nerve cell signals causes this disorder. Specific signals make nerve connections to cement memories while others allow irrelevant memories to be lost. This signaling system becomes imbalanced so that new memory connections are inhibited while more information is forgotten. Reversible metabolic processes may be involved in the early stages of AD.

Dr. Bredeson and his colleagues at UCLA believe that a comprehensive, personalized approach is the best way to treat memory loss. They have developed a program that optimizes diet (no simple carbohydrates, gluten, or processed foods), utilizes meditation and yoga, and emphasizes the importance of sleep, hormones, good oral health, and exercise. Patients may use supplements as well as medium chain triglycerides like coconut oil or Axona.

The researchers believe that free T3 and T4, estradiol, testosterone, progesterone, pregnenolone, and cortisol need to be optimized. Nine out of ten patients in this pilot program had cognitive improvement.

Additional Resources:

For more resources from Women’s International Pharmacy, see our Mental Health Resources page.

A New Treatment Program to Improve Memory Loss2018-04-04T15:44:16-05:00