The Blog

Featuring fresh takes and real-time analysis from HuffPost's signature lineup of contributors

T.S. Wiley Headshot

Estrogen Dilemma: There Is No Dilemma When You Know the Details

Posted: Updated:

Dying of Cancer is something we all fear.

Having a heart attack, although it seems more remote, because we don't hear about it on television every day, would probably kill us where we stand. But the possibility of losing our minds and independence and not even really knowing it is truly the most dreaded potential out there ahead of us.

Every day, we're all one day closer to Alzheimer's disease.

Over four million people suffer from Alzheimer's disease, which affects one in two people over the age of eighty. That means if you're in a room with one person right now, it will, sooner or later, down the line, be you or him.

And it's completely preventable, according to the gold standard of research. Dementia, memory loss, and Alzheimer's may, in fact, be preventable with natural hormones prescribed in a cycle that mimics the rhythmic, escalating, and descending doses your body naturally produced when you were young; this is not the case with conventional synthetic pharmaceutical HRT.

Hormones you biologically produced in your brain like estrogen and progesterone orchestrate, directly, and indirectly, your entire nervous system. Your nervous system, under the control of directives from the brain, includes your heart, stomach, liver, pancreas, and immune system. All of these organs were created from the neural crest when you were an embryo. The neural crest is the visible backbone of the tadpole fetus in the pictures of life in utero.

The cells of the neural crest divide and differentiate into your brain, heart, stomach, liver, and pancreas, all connected by your spinal cord to the outside world by your immune system.

All of these organs respond not only to sex hormones fitting into their own hormone receptors directly, but to proteins called neurotransmitters, such as serotonin, dopamine, and acetylcholine.

These neurotransmitters are the stop/start currency of cells called neurons in your brain and in target organs and muscles. All of the firing, the snap-crackle-and-pop of thinking moving, and even autonomic functions like lungs breathing and hearts beating, happens because of neurotransmitters and thereby directly because of hormones.

Hormones made in the brain can act too, locally, as avatar neurotransmitters; which are the cables and wiring along which firing happens. That fact is the reason that synthetic hormones and derivatives of hormones from another species like the horse cause such havoc in your body and brain.

You are hardwired for the "radio frequency" of sex hormones, insulin, melatonin and prolactin to read the environment, and literally, throw the switches on your behavior and thinking.

The main mechanism of destruction that ensues when you take Premarin isn't actually only caused by its weak estrogenic action. It's primarily caused by an immune response to Premarin due to cross-species reaction, because, for your body, it's foreign substance that actually puts your immune system on alert.

Synthetic Progestins, on the other hand, confuse all of your neurological systems because they have the supreme power to affect estrogen, progesterone, and testosterone receptors, but not in any natural or known template, because they are invented in a lab.

Progestins do not occur in nature.

Since all of the cells in your brain produce sex hormones from cholesterol, the entire nervous system from your head to your toes and fingers is really, itself, an endocrine system. And why estrogen and progesterone are classified as neurosteroids.

The Journal of Clinical Endocrinology and Metabolism, has in a review article sponsored by the Endocrine Society, reported that "estrogen maintains functions of key neural structures, such as the hippocampus and basal forebrain, and the widely projecting dopaminergic, serotongenic, and noradrenergic systems."

That's pretty much all of your brain.

They go on, "as estrogen levels decline over the menopause, these systems and the cognitive and other behavioral processes that depend on them also decline, at least functionally, yet they appear to respond to estrogen replacement." That means that running out of estrogen makes you display the behaviors that we all identify as "old," and putting estrogen back can reverse that.

Insulin resistance, getting fat and higher cholesterol levels in old age are a compensatory mechanism to produce more estrogen in the brain, since you make estrogen locally in your fat base, too, through an enzyme called aromatase.

Cholesterol becomes pregnelanone, then progesterone, then testosterone, and finally the testosterone converts through aromatase to the most active sex steroid in the brain--estrogen. The irony here is that the drugs for high cholesterol, osteoporosis, or cancer that will be prescribed to you as you age and get fat can cause brain injury in a myriad of other ways that can only exacerbate aging even further.

In fact, taking Lipitor, Tamoxifen, Raloxifene, or Arimidex will increase your chances of developing brain disease. Cholesterol-inhibiting drugs, by inhibiting the enzyme HMG-CoA-reductase locally in the brain, can cause dementia faster than normal aging can without drugs, because cholesterol is the precursor needed to make estrogen and progesterone in the brain. Tamoxifen, too, is well documented to cause brain damage and memory loss by blocking estrogen reception in the brain.

When doctors misuse testosterone as hormone replacement for women, it just seems to make you better because it converts to estrogen in the brain, just as our adrenal testosterone can as long as we have fat around. Remember, it takes some body fat to have aromatase, being thin is a deficit in making hormones. The trendy new aromatase inhibitors like Armidex now being used to block estrogen production in breast cancer must cause dementia in the long run--because testosterone converts to estrogen by way of aromatase, and it's estrogen that controls brain function primarily on its own and also through the generation of progesterone receptors.

In the brain, the high levels of escalating estrogen and progesterone in pregnancy have also been found to change the brain in some permanent fashion, too. That means pregnancy and lactation serve to developmentally design continuing brain health.

University of Richmond, Professor Craig Kinsley reported that, "Our research shows that the hormones of pregnancy are protective to the brain." His group's tests on rats show that those who raise two or more litters of pups do significantly better in tests of memory and skills than rats who have no babies, and their brains show changes that suggest they may be protected against such diseases as Alzheimer's, too. Kinsley concluded his report with, "It's rat data but humans are mammals just like these animals are mammals."

The brain's architecture is constantly being modified and remodeled by sex hormones, depending on the demands that it must meet. In order to retain the same plasticity of youth, your brain must be soaked in hormones that control all of the on and off switches as well as the maintenance routines. Sex hormones actually "activate and deactivate" the nervous system.

In adults, the effects of sex hormones are reversible, meaning... the effects only last as long as the hormone is around. It is exactly the same ups and downs of FSH, estrogen, LH, and progesterone that control ovulation and menstruation, that control myelination and demylenation of neurons simultaneously. The natural fluctuations in estrogen levels in youth stimulate a coordinated and dramatic reorganization of synapses and glia on a monthly basis. The cyclic rhythm of sex hormone production in young women unsheath and resheath axions and retracts neurons. The preovulatory surge in estrogen literally remyelinates the brain and body (spinal cord included) every month.

Taking these facts into consideration, you can see why losing your menstrual cycle can mean losing your mind in such an elaborate way.

An article published in the Journal of Neurobiology by Cynthia L. Jordan at Berkley states, "It is clear that exogenous estrogen produces the same effects." That means we should be able to get our minds and memories back with the correct hormone replacement. Bio-identical estradiol and progesterone dosed bio-mimetically should successfully restore lost youth in the brain.

For example: Progesterone modulates, among others, nicotinic receptors in the brain. Nicotine was so named because it affected these receptors. Nicotinic receptors use a neurotransmitter called acetylcholine, too. Acetylcholine is the neurotransmitter that enhances the flow of information from one neuron to another through synapses. This synaptic activity is the snap, crackle, pop of thinking. Cigarettes really do really help you to think more clearly. Synaptic function between neurons depends on cell adhesion molecules called e-cadherins that are controlled by estrogen. Estrogen is the "glue" between neurons that fosters synaptic plasticity (flexibility) and dendritic growth (branching out of neurons).

The big point here is that your brain, too, must have rhythmic blasts of estrogen and then progesterone repeatedly in different harmonies with other hormones--like thyroid, cortisol and human growth hormone, just like your breasts, ovaries, and heart to be healthy.

Overall, bio-identical hormones when delivered biomimically and monitored to be in sync with your body will have a dramatic effect on your whole mental balance as well as body balance.

Fan The Wiley Protocol on Facebook!

Source List

Zhang, F, et al. Synthesis and reactivity of the catechol metabolites from the equine estrogen, 8, 9-dehydroestrone. Chem Res Toxicol 2001; 14: 754-63.

Bethea, C, et al. Ovarian steroid action in the serotonin neural system of macaques. Novartis found Symp 2000; 230: 112-30.

Magnaghi, V, et al. Neuroactive steroids and peripheral proteins. Brain Res Brain Res Rev 2001; 37: 360-71.

Melcai, R, et al. Formation and effects of neuroactive steroids in the central and peripheral nervous system. Int Rev Neurobiol 2001; 46: 145-76.

Mercier, G, et al. Early activation of transcription factor expression in Swann cells by progesterone. Brain Res Mol Brain Res 2001; 97: 137-48.

McEwen, B. Clinical Review 108. The molecular and neuroanatomical basis for estrogen effects in the central nervous system. J Clin Endocrinol Metab 1999; 84: 17.

Warner, M, et al. Cytochrome P450 in the brain neuroendocrine functions. Front Neuroendocrinol 1995; 3: 224-36.

Meinhardt, U, et al. The essential role of the aromatase/p450arom. Semin Reprod Med 2002 Aug; 20 (3): 277-84.

Balthazart, J, et al. Rapid and Reversable Inhibition of Brain Aromatase Activity. Journal of Neuroendocrinology 2001; 13: 63-73.

Balthazart, J, et al. Phosphorylation processes mediate rapid changes of brain aromatase activity. J steroid Biochem Mol Biol 2001; 79: 261-77.

Honda, SI, et al. Characterization and purification of a protein binding to the cis-acting element for brain-specific exon 1 of the mouse aromatase gene. J Steroid Biochem Mol Biol 2001 Dec; 79 (1-5): 255-60.

Michalak, S, et al. Cholestrerol synthesis in the rat brain in course of late development as determined by 3-hydroxy-3-methylglutaryl CoA reductase activity. Folia Neuropathol 1996; 34: 7-10.

Kovacs, W, et al. Putrification of brain peroxisomes and localization of 3-hydroxy-3methyl coenxyme A reductase. Bur J Biochem 2001; 268: 4850-9.

Roher, A. Beta peptides and reduced cholesterol and myelin proteins characterize white matter degeneration in Alzheimer's disease. Biochemistry 2002; 41: 11080-90.

Islam, E, et al. Inhibition of rat brain prostaglandin D synthetase by 3-hydroxymethylglutamyl coenzyme reductase inhibitors. Biochem Int 1990; 22: 601-5.

Shefer, S, et al. Is there a relationship between 3-hydroxy-3-methylglutamyl coenzyme a reductase activity and forebrain pathology in the PKU Mouse? J Neurosci Res 2000; 61: 549-63.

Michikawa, M, et al. Inhibition of cholesterol production but not nonsterol isoprenoid products induces neuronal cell death. J Neurochem 1999; 72: 2278-85.

Choi, J. Lovastatin-induced proliferation inhibition and apoptosis in C6 glial cells. J Pharmacol Exp Ther 1999; 2898: 572-9.

Corsini, A, et al. Relationship between mevalonate pathway and arterial myocyte proliferation: in vitro studies with inhibitors of HMGF-CoA reductase. Atherosclerosis 1993; 101: 117-25.

Nishio, E, et al. 3-hydroxy-3-methulglumamyl coenzyme A reductase inhibitor impairs cell differentiation cultured adipogenic cells (3T3-L). Euro J Pharmacol 1996; 301: 203-6.

Choi, J. Lovostatin induces apopotosis of spontaneously immortalized rat brain neuroblasts: involvement of nonsterol isoprenoid cells (3T3). Eur J Pharmacol 2001; 408:2-6.

Michikawa, M, et al. Apolipoprotein E4 induces neuronal cell death unnovo cholesterol synthesis. J Neurosci Res 1998; 54: 58-67.

Koudinavo, N, et al. Alzheimer's abetal2-40 peptide modulates lipid synthesis in neuronal cultures and intact rat fetal brain under normoxic and oxidative stress conditions. Neurochem Res 2000; 25: 653-60.

Michikawa, M, et al. Inhibition of cholesterol production but not of nonsterol isoprenoid products induces neuronal cell death. J Neurochem 1999 Jun; 72 (6): 2278-85.

Ibid. Inhibition of cholesterol production but not of nonsterol isoprenoid products induces neuronal cell death. J Neurochem 1999; 72: 2278-85.

Owen, K, et al. Toxicity of a novel HMG-CoA reductase inhibitor in the common masrmoset (Callithrix jacchus). Hum Exp Toxicol 1994; 13: 357-68.

Ness, G. Developmental regulation of the expression of genes encoding proteins involved in cholesterol homeostasis. M J MED GENET 1994; 50: 355-7.

Mitchalak, S, et al. Cholesterol synthesis in rat brain in course of late development as determined by 3-hydroxy-3-methylglutaryl CoA reductase.

Xu, G, et al. Relationship between abnormal cholesterol synthesis and retarded learning in rats. Metabolism 1998; 47: 878-82.

Garcia-Peregrin, E. Contribution of brain and liver to the biosynthesis of cholesterol during the postnatal development of the chicken. Rev Esp Fisiol 1982; 38: 247-50.

Zhang, L, et al. Sex-related differences in MAPKs activation in rat astrocytes: effects of estrogen on cell death. Brain Res Mol Brain Res 2002; 103: 1-11.

McMillan, PJ, et al. Tamoxifen enhances choline acetyltransferase mRNA expression in rat basal forebrain cholinergic neurons. Brain Res Mol Brain Res 2002; 103: 140-5.

Meinhardt, U, et al. The aromatase cytochrome P-450 and its clinical impact. Horm Res 2002; 57: 145-52.

Jordan, C. Steroid hormone receptors after aromatase inhibition. J Steroid Biochem Mol Biol 1998; 65: 123-9.

Jordan, C. Glia as mediators of steroid hormone action on the nervous system. An overview. J Neurbiol 1999; 40: 434-45.

Blaschuk, OW, et al. E-cadherin, estrogens and cancer: is there a connection? Can J Oncol 1994 Nov; (4): 291-301. Review.

Bakarat-Walter, D. Differential effect of thyroid hormone deficiency on the growth of calretinin-expressing neurons in rat spinal cord and dorsal root ganglia. J Comp Neurol 2000 Oct 30; 426 (4): 519-33.

Hawkinson, JE, et al. Correlation of neuroactive steroid modulation of [355]t-butylbicyclophosphorothionate and [3H] flunitrazepam binding and gamma-aminobutyric acid A receptor function. Mer Pharm 1994 Nov; 46(5): 977-85.

Zinder, O, et al. Neuroactive steroids: their mechanism of action and their function in the stress response. Acta physiol Scand 1999; 167: 181-8.

Monks, DA, et al. Estrogen-inducible progesterone receptors in the rat lumbar spinal cord: regulation by ovarian steroids and fluctuations across the estrous cycle. Horm Behav 2001; 40: 1717-22. http://www.cizstarnet.com/health/womens/021108motherhood.shtml.

Mercier, G, et al. Early activation of transcription factor expression in Swann cells by progestereone. Brain Res Mol Brain Res 2001; 97: 137-48.

Gago, N, et al. Progesterone and the oligodendroglial lineage: stage-dependent biosynthesis and metabolism. Glia 2001; 36: 295-308.

Schumacher, M, et al. Progesterone synthesis and myelin formation in pereipheral nerves. Brain Res Brain Rev 2001; 37: 343-59.

Fields, R, et al. New Insight into Neuron-Glia Communication. Science 2002; 298: 556-62.

Minigar, A, et al. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurological disorders: HIV-associated dementia, Alzheimer disease, multiple sclerosis. J Neurol Sci 2002; 202: 13-23.

Fields, R, et al. New Insight into Neuron-Glia Communication. Science 2002; 298: 556-62.

Minagar, A, et al. The role of macrophage/microglia and astrocytes in the pathogenesis of the three neuroligical odiseasaes: HIV-associated dementia, Alzheimer disease, multiple sclerosis. J Neurol Sci 2002; 202: 13-23.

Blake, C. Effects of estrogen and progesterone on luteinizing hormone release on ovariectomized rats. Endocrinology 19977; 101: 1122-1129.

Jacobson, W, et al. Decreased in mediobasal hypothalamic and preoptic area opoid binding are associated with the progesterone-induced luteinizing hormone surge. Endocrinology 1989; 124: 199-206.

Krey, L, et al. The estrogen-induced advance in the cyclic LH surge in the rat: dependency on ovarian progesterone secretion. Endocrinology 1973; 93: 385-390.

Petersen, SL, et al. Differential effects of estrogen and progesterone on levels of POMC mRNA levels in the arcuate nucleus: relationship to the timing of LH surge release. J Neuroendocrinol 1993; 5: 643-48.

Sar, M, et al. Neurons of the hypothalamus concentrate (3H) progesterone or its metabolites. Science 1973 Dec 21; 182 (118): 1266-8.

Weiland, N, et al. Aging abolishes the estradiol-induced suppression and diurnal rhythm of propiomelanocortin gene expression in the arcuate nucleus. Endocrinology 1990; 131: 2959-64.

Chowen, JA, et al. Sexual dimorphisms and sex steroid modulation of glial fibrillary acidic protein messenger RNA and immunoreactivity levels in the hypothalamus. Neuroscience 1995; 69: 519-32.

Day, JR, et al. Gonadal steroids regulate the expression of glial fibrillary acidic proteins in the adult male rat hippocampus. Neuroscience 1993, 55: 435-43.

Del Cerro, S, et al. Neuroactive steroids regulate astroglia morphology in hyppocampal cultures from adult rat. Glia 1995; 14: 65-71.

Duenas, M, et al. Interaction of insulin-like growth factor-I and estradiol signaling pathways on hypothalamic neuronal differentiation. Neuroscience 1996; 74: 531-39.

Fernandez-Galaz, MC, et al. Role of astroglia and insulin like growth factor-I in gonadal hormone dependent synaptic plasticity. Brain Res bull 1997; 44: 525-31.

Frankfurt, M, et al. Estrogen increases axodendritic synapses in the VMN of rats after ovarietectomy. Neuroreport 1991; 380-2.

Friend, KE, et al. Specific modulation of estrogen receptor mRNA isoforms in rat pituitary throughout the estrous cycle and in response to steroid hormones. Mol Cell Endocrinol 1997; 131: 147-55.

Garcia-Segura, M, et al. Gonadal hormones as promotors of structural synaptic plasticity: cellular mechanism. Prog Neurobiol 1994; 44: 279-307.

Gu, Q, et al. 17 beta-Estradiol potentiates kainate-induced currents via activation of the cAMP cascade. J Neurosci 1996 Jun 1; 16 (11): 3620-9.

Jung-Testa, I, et al. Demonstration of steroid hormone receptors and steroid action in primary cultures of rat glial cells. Mol Biol 1992; 41: 621-31.

Murphy, DD, et al. Estradiol increases dendritio spine density by reducing GABA neurotransmission in hippocampal neurons. J Neuroscience 1998; 18: 2550-82.

Stone, et al. Directional transcription regulation of glial fibrillary acidic proteins by estradiol in vivo and in vitro. Endocrinology 1998; 139: 3202-9.

Garcia-Segura, LM, et al. Estradiol promotion of changes in the morphology of astroglia growing in culture depends depends on the expression of polysialic acid of neural membranes. Glia 1995; 13: 209-16.

Garcia-Segura, LM, et al. Gonadal hormone regulation of fibrillary acidic protein immunoreactivity and glial ultrastructure in the rat neuroendocrine hypothalamus. Glia 1994; 10: 59-69.

Naftolin, A, et al. Neuronal membrane remodeling during the oestrus cycle: a freeze-freacture study in the arcuate nucleus of the rat hypothalemus. J Neurocytol 1988; 17: 377-83.

Garcia-Segura, LM, et al. Astrocytic shape and glial fabrially acidic protein immunoreactivity are modified by estradiol in primary rat hypothalamic cultures. Dev Brain Res 1989; 456: 357-63.

Hatton, P, et al. Function-related plasticity in hypothalamus. Ann Rev Neurosci 1997; 20: 375-97.

Hyden, H, et al. Satellite cells in the nervous system. Sci Am 1961; 205: 62-70.

Langub, MC, et al. Estrogen receptor immunoreactive glia, endothelia and ependyma in guinea pig preoptic area and median eminence: electron microscopy. Endocrinology 1992; 130: 364-72.

Mong, JA, et al. Estrogen mediates the hormonal responsiveness of arcuate astrocytes in neonatal rats. Soc Neurosci 1998; Abstr 24: 220-5.

Perducz, A, et al. Estradiol induces plasticity of GABAergic synapses in the hypothalamus. Neuroscience 1993; 53: 395-401.

Perez, S, et al. The role of estradiol and progesterone in phased synaptic remodeling of the rat arcuate nucleus. Brain Res 1993; 6508: 38-44.

Santagati, S, et al. Estrogen receptor is expressed in different types of glial cells in culture. J Neurochem 1994; 63: 2058-64.

Shughrue, A, et al. Comparative distribution of estrogen receptor alpha and--beta mRNA in the rat central nervous system. J Comp Neurol 1997; 388: 507-25..

Sison, F, et al. A potential influence of ovarian cycle day on the presence of polysialic acid neutral cell adhesion molecule (PSA-NCAM) in the rat hypothalamus. Soc Neurosci 1997; Abstr 23: 770-4.

Torres-Aleman, I, et al. Estradiol promotes cell shape changes and glial fibrillary acidic protein redistribution in hypothalamic astrocytes in vitro: a neuronal-mediated effect. Glia 1992; 6 (3): 180-7.

Wooley, P, et al. Estradiol mediates fluctuation in hyppocampal synapse density during the estrous cycle in adult rat. J Neurosci 1992; 12: 2449-54.

Wooley, P, et al. Estradiol regulates hippocampal dendritic spine density via an N-methyl-D-aspartate receptor mechanism. J Neurosci 1994; 14: 7680-87.

Wooley, P, et al. Estradiol increases the frequency of multiple synapse boutons in the hippocampalcal region of the adult female rat. J Comp Neurol 1996; 373: 108-17.

Wooley, P, et al. The molecular and neuroanatomical basis for estrogen effects in the central nervous system. J Clin Endocrinol Metab 1999; 84: 1790-7.

Jordan C. Glia as mediaters of steroid hormone action on the nervous system. An overview. J Neurobiol 1999; 40: 434-45.

Temburni, MK, et al. Receptor Targeting and Heterogeneity at interneuronal nicotinic cholinergic synapses in vivo. Journal of Physiology 2000; 525.1: 21-29.

Quattrocki, E, et al. Biological Aspects of the Link Between Smoking and Depression. Harvard Rev Psychiatry 2000 September; 99-110.

Mong, JA, et al. Steroid-induced developmental plasticity in hypothalamic astrocytes: implications for synaptic pattering. J Neurobiol 1999; 40: 602-19.

Hilschmann, G, et al. The immunoglobulin-like genetic predetermination of the brain: the protocadherins, blueprint of the neuronal network. Naturwissenschaften 2001; 88: 2-12.

Bakarat-Walter, I, et al. Role of thyroid hormones and their receptors in pereipheral nerve regeneration. J Neurobiol 1999; 40: 541-59.

Valera, S, et al. Progesterone modulates a neuronal nicotinic acetylcholine receptor. ProcNatl Acad Sci (USA) 1992; 89: 9949-53.

Changeux, J. The TIBS lecture; the nicotinic acetylcholine receptor: an allosteric protein prototype of ligand-gated ion channels. Trends Pharmacol Sci 1990; 11: 485-92.

Smith, SS. Progesterone administration attenuates excitatory amino acid responses of cerebellar Purkinje cells. Neuroscience 1991; 42 (2): 309-20.

Bertrand, D, et al. Steroids inhibit nicotinic acetylcholine receptors. Neuroreport 1991; 2: 277-80.