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How Hormones Interact with each other

Excerpt from Discussion section of Ph.D Dissertation on Bio-identical Hormones Dr. Richard Nkwenti; R.Ph; IMD; Ph.D

Hormone restoration is plagued by numerous controversies and misinformation often without unproven data partly because the medical community does not differentiate between what constitutes synthetic hormones and what constitutes bio-identical hormones. Looking at these case studies, we find that most patients had estrogen dominance, when the amount of available estrogen surpasses the amount of available progesterone. When this occurs, the endocrine system underperforms leading to such symptoms as if Fibrocystic, irregularity of menstrual flow, weight gain, vasomotor symptoms, anxiety, irritability, and other changes. Estrogen dominance becomes even severe is made worst by women who do not ovulate or those who have had significant exposure to synthetic estrogens. Improper metabolism of estrogens also plays a role. DIM (Diindolylmethane) dietary supplements incorporated into the hormone balance regimen of any and all patients with hormone balance issues seems to answer the call due to its ability to modulate the way estrogens particularly estradiol is metabolized in the human body (Rajoria et al., 2011). Of great significance in this study is the fact that although most patients were unable to readily lose any significant weight even though most of their symptoms disappeared, there is a bigger need to evaluate thyroid function using a Functional and integrative medicine approach. Why is this important? Because thyroid gland malfunction has the capability to cause significant weight gain. Using the conventional blood analysis which looks at TSH levels, and T4 (free or non-free) levels as a measure of thyroid function is inadequate. We must therefore thus look at the complete picture which involves Free T4 levels, free T3 levels, Thyroid peroxidase levels for autoimmune antibodies, TSH, reverse T3 etc. The thyroid gland controls virtually all metabolic processes in the human body. It determines the rate at which we burn calories. The heart of thyroid functioning lies on the amount of active free T3 (Liothyronine) levels. Most patients on the low side of free T3 level (Normal levels 2.3-4.2 pg/mL) are not functioning to the maximum. Hence, efforts must be made by the practitioner to get to the root cause of low T3 levels, most particularly the lack of essential nutrients such as Selenium, Zinc, and chromium. Zinc and selenium are two essential minerals required for T4-T3 conversion. For this conversion to work, one of the main enzymes relies on selenium. These are vital nutrients for the conversion of T4 to T3. T4 (Levothyroxine) is a prohormone, and as such it must be converted in the human body to T3 through deiodinases. This process is ineffective and slow in the absence of essential nutrients such as Chromium, selenium, and iodine. If the thyroid is not functioning properly, it can contribute to weight gain, fluid retention, hair loss, depression, constipation etc. The thyroid is the organ with the highest selenium content per gram of tissue, expressing specific selenoproteins. Enough selenium has been found to be associated with weight loss (Wang et al., 2016), The value of Selenium supplementation goes a long way on our hormone replacement patients with weight gain issues after evaluating their thyroid function and possibly their selenium levels. Most authors - 129 - attribute supplementation's effect on the immune system to regulating reactive oxygen species production and their metabolites. 

A major finding in this study is how helpful progesterone is for the restoration of vital functions in the human body. The form and dosage form used is important due to the way progesterone works with metabolites of progesterone playing a vital role in their metabolic actions. Transdermal progesterone in a nutshell is the preferred method for using progesterone for HRT partly because it does not pass through the stomach and liver where about 90% of the progesterone is broken down to inactive metabolites. The only reason why other oral forms of progesterone specifically Progesterone in Olive oil capsules and Oral Liposomal Progesterone (as used in this study on a few patients) is because of the need to rapidly increase blood levels of this hormone, and the need to help patients get a better night’s sleep. At a significantly reduced dose, Liposomal oral progesterone seems to be a solution to consider for practitioners looking to raise the blood levels of progesterone quickly. It is formulated into an oil-based capsule dosage form using sunflower lecithin incorporated into liposomes for enhanced absorption and improved bioavailability. This is possibly an area of interest to many practitioners worldwide because of the crucial role played by progesterone in the human body. However, more studies are needed to measure bioavailability, comparative analyses of saliva, serum, and blood levels of liposomal progesterone after several months of treatment. 

The medical literature on postmenopausal women's use of progesterone is often confusing, contradictory, and misleading. A vast majority of physicians are of the opinion that progesterone may increase the risk of breast cancer. In fact, there do not seem to know the difference between Natural bioidentical and synthetic progesterone or progestins. Natural progesterone has a chemical structure, which is vastly different from the chemically altered, synthetic chemicals called progestins, resulting in different cell-level actions. Synthetic progestins for the most part are unable to stimulate the same receptors as natural bioidentical progesterone. Natural progesterone is significantly different structurally and functionally from synthetic progestins. Progestins do not balance estrogen, and thus in fact interfere with the body’s own production of natural bioidentical progesterone.  Synthetic progestins may be associated with conditions such as increased appetite, weight pain, fluid retention, depression, decreased energy, migraines, breast tenderness, decrease libido, hair loss, protection of the uterus and not the breast from breast cancer and ability to counteract a great deal of the positive effects of estrogen on serotonin (Sinatra, Houston, & American College of 2015, p. 357). On the other hand, some synthetic estrogens and progestins are almost 200 times more potent than their natural counterparts on a weight to weight basis which makes their ability to promote growth of cancer cells significant. The benefits of using natural progesterone, unlike synthetic progestins cannot be ignored such as the ability to create a balance between estrogen and progesterone and avoid estrogen dominance, the ability to lower blood pressure, ability to improve sleep hygiene, ability to calm the body naturally, the ability to lower cholesterol and eliminate fats, ability to protect from breast cancer through its antiproliferative effect. Other actions include potentials to increases scalp hair, increases metabolic rate, ability to function as a natural antidepressant, production of new bone and ability to enhance the action of thyroid hormones (Sinatra et al., 2015, p. 358).

 Estrogen for hormone replacement therapy functions at their maximum efficiency when both estradiol and estriol are incorporated in the same formula because both hormones have a positive effect on the heart. Estradiol when applied transdermally has been shown not to have any effect in increasing risk of developing any cardiovascular accident or thromboembolism (Speroff, 2010), (Canonico et al., 2007), (Scarabin et al., 1997). Synthetic estrogens do not have the same chemical structure as the natural bio-identical estrogens produced by the human body thus making such “drugs” unable to fit into the estrogen receptors exactly the way natural estrogens are supposed to fit. Case in point involves natural Estradiol (E2) produced naturally in the body is typically removed within a few hours compared to conjugated equine estrogens that have been shown to stay in the body for up to thirteen weeks due to the lack of metabolizing enzymes to break it down for elimination. It is also worthwhile noting that some synthetic estrogens are up to 200 times more potent than their natural counterparts (Rakel, 2012, p. 1250).  It is evident in this study why almost all patients have had a before and after results via laboratory testing and dual survey results from the laboratory performing the laboratory findings and another result from the researcher showing mostly an improvement in the symptoms where estrogens play a crucial role in their restoration. Estradiol in particular plays a role in maintaining potassium levels, promotes calcium absorption, promotes magnesium, and zinc uptake and use; increases high-density lipoprotein; helps decrease low low-density lipoprotein and total cholesterol; helps reduce triglycerides when administered through the transdermal route as used in these studies; helps decrease platelet stickiness, which may make the need for warfarin or other antiplatelet drugs obsolete if the physician chooses to do so. Studies have also shown that Estradiol increases growth hormone, increases serotonin; which may make the use of certain antidepressants obsolete; Helps in the maintenance of bone structure thus making it a powerful prevention strategy against osteoporosis. Other benefits of estradiol worth mentioning are helps in increasing blood levels of endorphins. Endorphins are chemicals that the nervous system generates naturally to cope with pain or stress. They are often called "feel-good" chemicals because they can act as a reliever of pain and a booster of happiness.

Endorphins are produced primarily in the hypothalamus and pituitary glands although they may also come from other parts of the body. Estradiol helps decrease fatigue, helps prevent memory loss and acts as a natural antioxidant. Why then do health professionals oppose the use of Bio-identical hormone restoration? The summary to a long and complicated answer is simple; “ignorance”. According to Dr Pamela Smith from her groundbreaking book (what you must know about bioidentical hormones) and the author of chapter 35 (Integrative medicine 3rd edition) (Rakel, 2012), she explains why estrogens are better off not taken by mouth for hormone replacement or restoration. Estrogen prescribed for hormone restoration should be applied transdermal rather than orally because otherwise will potentially cause elevated blood pressure, ability to increase the prothrombotic effects; ability to increase triglycerides, ability to increase estrone, which is not needed at all during menopause and beyond, its ability to cause gallstones (Uhler, Marks, Voigt, & Judd, 1998), elevate liver enzymes, decrease growth hormone, interrupt tryptophan and serotonin metabolism. There is a high probability that oral HRT has the capability to increase C-reactive protein, liver enzymes and a decrease in the growth hormone. Thus, the evidence is clear this study was done using transdermal bio-identical hormones except for oral progesterone. Epidemiologic studies have shown that estrogen replacement therapy has the possibility of reducing heart disease by up to 50% in postmenopausal women with up to 40%-50% reduction in cardiovascular morbidity and mortality when estrogen is correctly used in any hormone restoration course. Also, Estradiol (E2), increases angiogenesis and the vasodilatation and helps in the reduction of Reactive oxygen species (ROS), oxidative stress and fibrosis, thus helping mediate its cardioprotective actions. Through these actions, E2 orchestrates the reduction of cardiac remodeling and ultimate attenuation of heart hypertrophy (Iorga et al., 2017). Results from this case studies support the fact that transdermal estrogens help painful musculoskeletal conditions such as arthritis, fibromyalgia, migraines etc as the perception of pain control as reported in the survey questionnaire shows some remarkable pain reduction. Transdermal application of estrogen has proven effective as a potential anti-inflammatory agent (Au et al., 2016) and osteoarthritis (Roman-Blas, Castaneda, Largo, & Herrero-Beaumont, 2009). Of consideration is also the ability of transdermal estrogen replacement to lower levels of interleukin (IL)-6, tumor-necrosis factor (TNF)-a and interleukin 1(IL-I) (Puder, Freda, Goland, & Wardlaw, 2001).