We now have seen several ME/CFS and Long COVID cases that have gotten noticeable improvement with the following approach and observations.
Disclaimer
At the outset, I would like to emphasize that the following considerations are purely hypothetical and intended as a contribution to discussion, not as a scientifically validated theory.
However, when dealing with patients who often move from one physician to the next without clear answers, even preliminary ideas and clinical hypotheses may offer useful perspectives for the wider medical community.
What we observed
The background information comes from my brilliant HP Tobias Eisenknapp, who has completed extensive hormone training and has been practicing hormone therapy for 15 years.
Tobias has a photographic memory and he loves
1) doing research regarding background of diseases
2) “bizarre, unusual” cases.
Thanks to his interesting laboratory tests (urine analysis = urinalysis) and especially his successful treatments of patients that are usually affected for years and have seen a considerable number of physicians before, he has become the star in our practice which means that all my staff go to Tobias, not me!
Background – Personal Health Journey
Tobias himself experienced significant health challenges related to long-term antiepileptic medication use during childhood, which led to severe liver stress. Over time, he developed a range of chronic health problems including fibromyalgia-like pain, elevated cholesterol levels, metabolic syndrome, and profound fatigue. The fatigue became so severe that he was forced to close his medical office in Munich several years ago.
While increasingly working in the field of hormonal imbalances, Tobias eventually discovered that he himself had markedly reduced free testosterone levels. This finding led him to investigate physiological ways to restore hormonal balance. He developed a method aimed at stimulating endogenous testosterone production, avoiding external testosterone supplementation, which can suppress Leydig cell function.
After implementing this approach, Tobias observed a remarkable improvement in his own health. His free testosterone levels increased, and over time many of his long-standing symptoms improved simultaneously. With regular laboratory monitoring performed monthly, he documented progressive normalization of several metabolic markers, including cholesterol levels and HbA1c. His chronic pain resolved, and his energy levels returned to normal.
Reminds me of Sir Petros Kattou
Sir Petros (knighted KStMW last year in recognition of his contributions to humanity) developed the SOZO Method of Functional Brain Network Analysis and Modulation (FNON) after personally suffering for many years from excruciating pain caused by CRPS, FBSS, and fibromyalgia. After undergoing hundreds of unsuccessful treatments — including 12 surgeries performed in vain — he eventually succeeded in dramatically improving and ultimately resolving his condition through the use of various neuromodulation modalities.
Every patient who did not improve under Petros’ FNON treatment became a motivation for further research. He continued to investigate, refine, and adapt the method until he was able to improve that patient’s condition.
After many years of research, Petros formally registered the SOZO Method of Functional Brain Network Analysis and Modulation (FNON). The method is now being progressively published in peer-reviewed medical journals. Because Petros has treated thousands of patients, many of whom experienced substantial improvement or near complete resolution of symptoms, numerous scientific publications based on these clinical experiences are expected in the coming years.
Back to Tobias
Hormonal Imbalances as Possible Co-Factors in Chronic Disease
In recent years we increasingly observe hormonal imbalances as potential co-factors in many chronic diseases. The careful wording “we seem to find more and more…” reflects the reality of how clinical knowledge develops in everyday medical practice.
A physician may initially encounter a new observation or therapeutic approach that clearly benefits a single patient. When similar patients present with comparable symptoms, the physician naturally begins to look for shared patterns or underlying mechanisms. If similar laboratory findings are identified and targeted interventions lead to improvements both in symptoms and in laboratory parameters during follow-up, this gradually forms the basis for a working clinical hypothesis that can guide treatment in future patients.
This process represents a form of continuous clinical learning. Physicians constantly refine their understanding through observation, diagnostic testing, therapeutic trials, outcome evaluation, and reassessment. In practice, medicine therefore involves a continuous process of self-education and iterative clinical reasoning.
Although I have studied hormone therapy at five different institutions (Römmler, Rimkus, Douwes, Huber, and Metka) and have read 67 books on hormone replacement therapy (HRT) over the past 18 years, many of Tobias’s considerations were new and highly interesting to me.
Key insights include the importance of evaluating multiple hormonal parameters:
- Blood hormone levels remain essential, particularly
- SHBG (Sex Hormone Binding Globulin)
- FSH (Follicle-Stimulating Hormone)
- LH (Luteinizing Hormone)
- Prolactin
- Salivary hormone measurements provide important additional information because they reflect the biologically active free hormone fraction.
In several patients we observed situations where elevated SHBG levels bound most circulating hormones, leaving very little free hormone available. In such cases, blood levels of estrogen and progesterone may appear normal, yet patients can clinically present with symptoms resembling “pseudo-menopause.”
The practical conclusion from these observations is clear:
- Both blood and saliva hormone measurements should be evaluated, since relying on blood levels alone may miss clinically relevant deficiencies in free, biologically active hormones.
Tobias improvements of patients symptoms based on research studies suggest: Hormonal imbalances could be involved in:
- Fibromyalgia (= muscular rheumatism), joint pain, osteoarthritis
- Leaky gut – just like
- Anxiety, wired but tired,
- Weakness, fatigue….
- MCAS (!!!)
- Neurological disorders, dopamine deficiency, …..
- Vagus/sympathetic dystonia
All of this could be related to hormonal imbalances. Why? Please refer to the first sentence of this section: we seem to get more and more reliable hints due to the cycle of lab measurements – optimizing – clinical improvments – lab improvements in the patients that Tobias sees exclusively (which usually do not come to me to do Neuromodulation).
What “we” all did before: simply increasing progesterone based on blood test results indicating “estrogen dominance” seems to be insufficient. This is especially true if saliva tests show a deficiency of free DHEA, estrogen, or testosterone, even if these levels are present in sufficient quantities in the blood.
Example 1: Boy with Long COVID
A now 14-year-old boy who has been bedridden for three years since contracting COVID, not only due to fatigue with PEM but also because of excruciating muscle pain. This was the first case of PEM-positiv and GPRAAB – positiv LongCovid – which are the 2 criterias that I need to accept this diagnosis.
Now we got him out of bed last year for a few months with taVNS + tDCS neuromodulation, but then he had another COVID relapse, followed by endless muscle pain and PEM / Fatigue again and our ongoing neuromodulation was insufficient (probably due to lack of knowledge).
The boy tested positive for all the GPRA antibodies in the IMD lab, indicating an autoimmune disease against the energy receptors.
Now currently, there’s no accepted treatment for this problem, actually most of the clinics still think that this is a “mental problem” and prescribe antidepressive medications (really – March 2026, every week we hear such stories)
Off-label case-studies suggest improvement of ME/CFS and LongCovid by HELP Apheresis or Immunoadsorption Apheresis,
He was being denied Apheresis because he’s too young!
Of course the boy also has chronic recurrent herpes and EBV, and his father is also suffering from fatigue since contracting mumps as an adult some years ago. Both are basically “bed ridden” if their symptoms aggravate.
Tobias found a significant testosterone deficiency in the boys saliva—not in his blood—corrected this, and we treated the viruses with Valacyclovir and activated the pituitary gland and hypothalamus with several sessions of beloved Neuromodulation – SOZO – TPS.
Only one week later, the following WhatsApp message arrived (see image above).
Example 2 – Irritable Bowel Syndrome, Panic Attacks, Insomnia, Migraines, FMS
A 57-year-old female patient has had spastic colitis with watery stools for 20 years, extremely painful abdomen, anxiety, fatigue, complete insomnia (she can go a whole week without sleeping at all), migraines, fibromyalgia pain…
Tobias diagnoses a hormonal imbalance and, consequently, Mast Cell Activation Syndrome (MCAS).
He researched that mast cells become overactive when there is an estrogen deficiency.
He continued his research and finds an “old antihistamine” that can cross the blood-brain barrier which I prescribed.
The following night, and ever since, the patient has been sleeping through the night. Due to the hormone correction, the MCAS will gradually disappear; the muscle pain and irritable bowel syndrome have already resolved.
Tobias diagnoses a hormonal imbalance and, as a result, mast cell activation syndrome (MCAS).
A month after the patient was already doing well (she’s international, comes from one of the richest families in India, and has 20 years of prior treatment in Swiss clinics, the Mayo Clinic, etc.), she calls us and tells us that “Klinghardt has now also confirmed that hormones influence MCAS, and she’s feeling particularly good now.” We laugh—at the same time, I’m a little annoyed!
I have not seen this patient, of course we would have targeted brainstem (Raphe, Locus coeruleus) and the TMN of diencephalon with various SOZO-Neuromodulation-Modalities but I just know the case from Tobias.
Documentation and Future Scientific Publication
In the future, we aim to publish such clinical observations and treatment outcomes in appropriate scientific journals. To support this goal and ensure proper scientific documentation, we have begun implementing standardized clinical scoring systems for many patient.
These structured scores allow us to objectively measure baseline symptoms and follow-up improvements, providing quantifiable data on treatment outcomes. In addition, we document selected cases through video testimonials, which help illustrate functional changes and real-life improvements experienced by patients.
OK, this will be the future
and of course documentation is far beyond the normal pay-grade of a small countryside GP office as I am running it.
Now: running scores, collecting structured data and much more – just to be accepted by those peers that could not resolve this cases and just prescribe antidepressive medications??
Do I personally care that much about the approval of the so-called “scientific community”?
To be honest, not at all.
Over the course of my professional life I have seen too many examples where science — or what is presented as science — has disappointed its own ideals. Hoax studies, questionable statistics, industry-funded trials with obvious bias, and the firm tendency to ignore real-world clinical experience when it does not fit established narratives – as older I get as less I am able to ignore that.
Still, Petros keeps reminding me that if we want to be taken seriously, we have to play by proper scientific rules.
Kind of weired after he himself has developed everything “off-label” in “single case trials” creating theories by “interesting observations” doing “unconventional experiments” on normal patients. Anyways, live is complicated!
Conclusion
Tobias tells me about similar cases at least three times a week. I always tell him, “Please write this down. If you’re doing a seminar on these ‘findings,’ you’ll have to present the cases. Did you take photos of the patients or conduct video interviews?”
We have the feeling that we’re really onto something here. It is well known that ME/CFS and Long COVID affect the HPA axis.
In many of these Longcovid patients, we also find a clinical aldosterone deficiency (which is not clearly reflected in blood tests, but we don’t have a saliva test for it) and an improvement with a “mini-dose” of fludrocortisone—especially in POTS/PONS cases.
What makes this approach so exciting is the measurability in lab tests, the improvement of symptoms after lab-based correction, and the subsequent improvement also shown in lab results—which gives us the confidence that we are not working in some “alternative holistic medicine fog,” but rather doing sound clinical work.
Our problem is also Mainstream Medicine
that we don’t have a clinic where we can perform tests like the ACTH test.
At the endocrinology department of a nearby university hospital, for example, all these patients—even when we refer them for evaluation—are only given antidepressants.
We will probably have to perform these diagnostic tests ourselves (if anyone knows a specialist or department, please let us know).
Tobias will be giving a seminar soon
A two-day seminar, probably at the end of May or in June—I will announce it in good time. Tobias will then share the urine test and these hormone analyses with colleagues (doctors, naturopaths).
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