Hormone and pro-hormone therapy

Due to the nature of chronic disease, it is common for patients suffering from chronic diseases to have low levels of hormones. This is often due to high levels of the vitamin D metabolite 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. which interferes with the production of hormones such as T3, testosterone, etc. Because the vitamin D system is dysregulated in chronically ill patients, supplementing with other hormones tends to further dysregulate the receptors rather than increase hormonal expression. Thus, hormone supplementation is contraindicated. If the patient is already on hormone “replacement” therapy, judicious use of low-dose hormone therapy (to relieve intolerable symptoms) may be necessary until the patient is able to wean from the hormones.

Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (MP) patients are advised to work with their doctor to use the lowest dose of medication that is effective.

As patients begin to kill the Th1 pathogensThe community of bacterial pathogens which cause chronic inflammatory disease - one which almost certainly includes multiple species and bacterial forms. causing their disease, vitamin D metabolism restabilizes and 1,25-D's effects on hormonal stabilization becomes less of an issue. Once this happens, there is no longer a need to take extra hormone supplements, and patients can then wean off their steroids.

Overview of how steroid hormones work

Steroid hormones are molecules produced and secreted by endocrine glands in the body. These hormones are released in the blood stream and travel to other parts of the body where they bring about specific responses from specific cells. Steroid hormones are derived from cholesterol and are lipid-soluble molecules.

Steroid hormones cause changes within a cell by first passing through the cell membrane of the target cell. Once inside the cell each steroid hormone primarily binds with its specific receptor in the cytoplasm of the target cell. The receptor-bound-steroid-hormone then translocates into the nucleus of the cell. The steroid-receptor complex causes the production of messenger RNA (mRNA) molecules from DNA genes through transcription. The mRNA molecules are then transported to the ribosomes. The mRNA molecules code for the production of proteins through translation.

Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestagens. Vitamin D derivatives are a sixth closely related hormone system with homologous receptors, though technically sterols rather than steroids.

Types of hormone supplementation

The following types of hormone supplementation are discussed:

High 1,25-D interferes with the production and activity of other hormones

Hormone replacement therapy upsets cellular homeostasis

When a patient takes exogenous (supplemental) hormones including the male, female, and thyroid hormones, those hormones enter the blood stream with some leaching into the cell. It is not known how exactly hormones affect activity of the body's nuclear receptors. However, it may be the case that just as with elevated levels of 1,25-D, the presence of supplemental hormones triggers a feedback pathway which leads to reduced production of that hormone.

For example, if a patient is given testosterone, some of that testosterone enters the cell. Increased levels of testosterone may reduce the transcriptional activity of the Androgen Receptor, the nuclear receptorIntracellular receptor proteins that bind to hydrophobic signal molecules (such as steroid and thyroid hormones) or intracellular metabolites and are thus activated to bind to specific DNA sequences which affects transcription. which produces it. One possibility is that with reduced production of testosterone, the Androgen Receptor also reduces transcription in other ways, leading to a reduction in the production of certain families of antimicrobial peptidesBody’s naturally produced broad-spectrum antibacterials which target pathogens., which many active Type I nuclear receptors also produce.2) Therefore, hormone replacement therapy may compromise innate immune function in dose-dependent fashion. Research is needed to validate this theory.

Research into estrogen plus progestin therapy showed increased risks, 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers. (16608 healthy postmenopausal women studied over 5 years) 3)

To use hormone replacement therapy or not

Discontinuation of hormone supplements is not required for MP patients as long as the extra hormones are making up for a marked deficiency observable on a blood test. However:

There is a big difference between a body's hormonal control system producing a hormone under feedback control, and an attempt to change the operation of the control system by supplying exogenous drug (HRT). Another example is the use of exogenous Prednisone or cortisol to try and modulate the immune system - it is fraught with secondary problems.

Trevor Marshall, PhD

Many symptoms attributed to hormonal imbalance are actually due to immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed.. Before a patient assumes she needs HRT (hormone replacement therapy) she should be sure to try the suggestions for managing immunopathology.

For those patients and their doctors who decide to use HRT, the prevailing recommendation is to take hormones at the lowest effective dose only as needed for intolerable symptoms unrelieved by management of the MP medications. Reports suggest that a bio-identical product is preferable.

It is impossible to know for sure what effect using HRT has on the recovery process but sometimes compromises must be made in order to be comfortable enough to stay on the MP and make any progress.

Weaning from hormone therapy

As patients begin to kill the Th1 pathogens causing their disease, vitamin D metabolism restabilizes and 1,25-D's effects on hormonal stabilization becomes less of an issue. This means over the course of treatment, patients who could not produce adequate thyroid hormone begin to produce it naturally. Once this happens, there is no longer a need to take extra hormone supplements.

My suggestion would be to wean a steroid down slowly, and see what the effect is, bit by bit.

Trevor Marshall, PhD

Patients experiences

When I started the MP, I was also taking DHEA, pregnenolone, progesterone and testosterone. When I tested them again in December, the DHEA and pregnenolone were back to normal and I had to reduce the progesterone! I was able to stop progesterone and testosterone a few months ago as well!


My wife gets HRT due to surgery to remove fibroid tumors. She's had to lower the dose to the smallest available while on the MP. HRT is simply sometimes necessary, and the MP can be done in combination with the HRT. However, you do need to be able to change the dose level of the HRT as the MP changes things.


Soon after I got sick in '09, after going through what I thought was menopause, a doctor I was seeing got me onto Bio-Identical progesterone and estrogen Creams. It was call the Wylie Protocol. I began having cycles again like I did when I was in my 20's.

When I started the MP about a year ago, I abruptly stopped the progesterone but continued the estrogen. My cycles dissipated and stopped completely. I slowly weaned off the estrogen and have not used either for I think about 5 months now.

My epiphany is that, If I had not gone onto the Wylie Protocol, and forced my body to cycle, maybe by now, my body would have corrected itself. Due to my forcing things along I think I may have cost some time in my own healing.

I am having hints of PMS symptoms now and then and I do believe I will cycle again, in time, but I think, if I had not used estrogen and progesterone supplementation, my body would have already corrected in this area.

All other areas of my body are showing massive improvements after 10 months except in the female department. I am hoping this will improve soon also.

I write this, not to beat myself up for using assistance but to let anyone else in on my epiphany that is thinking about using hormone replacement therapies. IMO, our bodies know what to do.

They will return to normal balance even faster if we don't interfere.

CousinTC, MarshallProtocol.com

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===== References =====

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Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SAA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. doi: 10.1001/jama.288.3.321.
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