This, from www.news-medical.net (uploaded September 10, 2024), an article entitled “Liraglutide for Children 6 to <12 Years of Age with Obesity – A Randomized Trial”: the PMID is 39258838 and the DOI is https://doi.org/10.1056/nejmoa2407379
Abstract (selected text copied, verbatim)
Background: No medications are currently approved for the treatment of nonmonogenic, nonsyndromic obesity in children younger than 12 years of age. Although the use of Liraglutide has been shown to induce weight loss in adults and adolescents with obesity, its safety and efficacy have not been established in children.
My conclusion
Basically, this article says that Liraglutide is safe for children and works well, to reduce obesity and it recommends prescribing the drug to children as young as 6 years of age, although it makes no mention of any attempt to diagnose the cause of the children’s obesity and no consideration of the idea that if a treatable cause were found, the children could be returned to normal health without starting them on a lifetime course of a very expensive and possibly dangerous medication.
However it makes no mention of metabolic studies of any sort and particularly, no mention of the stress-related hypothyroidism, intracellular hypothyroidism, which is the hormonal/metabolic aberration most likely to be associated with obesity, whether childhood or adult.
This upsets me!
I find it distressing, that trained, expert physicians regard it as normal practice, to state that “Liraglutide’s safety and efficacy have not been established in children” and then to prescribe a months-long (perhaps lifelong!) course of Liraglutide to undiagnosed children!
It is even more distressing that the folks at clinicaltrials.gov would blithely issue a permit for a major investigation of unsuspecting children, in a format which does not include finding a diagnosis, before enrolling them in a trial of a new, untested drug.
Treatment with Metformin, beginning less than 4 days following onset of symptoms, reduced long COVID incidence by about 41%, compared with placebo.
This article, whose importance has been downgraded by the reduced incidence of severe Covid disease, is perhaps somewhat less cogent now than it was a year ago, but whose interest, and possible application to future viral diseases, was added to my original website on September 28, 2023.
The observation, which at the time created a stir in “Covid sciences” circles, was noticed and reported on 3/7/23, when it was still at the “preprint” stage: many news feeds carried it.
I have eliminated Scientific terminology and the fine details of the trial protocol, so as to render this very important article easier to understand, by my readers.
The full article was published by CT Bramante et al., on 6/8/23. In case you want to read it, here are the particulars: “Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial”, by Carolyn T Bramante, MD, Prof John B Buse, PhD, David M Liebovitz, MD, Jacinda Nicklas, MD, Michael A Puskarich, MD, Ken Cohen MD, Published: June 08, 2023. DOI: https://doi.org/10.1016/S1473-3099(23)00299-2
The authors tested treatment with Metformin, Ivermectin or Fluvoxamine, beginning at 3 days or less following onset of Covid 19 symptoms, to see whether any of those medications would reduce the severity of Covid. Later, the data was applied to the question of reducing the risk of Long Covid, with Metformin.
Trial protocol
A randomized, quadruple blind study was done at 6 sites in the US: overweight or obese adults, age 30 to 85 years, who had active Covid infection, were randomly assigned to receive one of the following combinations: metformin + placebo, ivermectin + placebo, fluvoxamine + placebo metformin + ivermectin, metformin + fluvoxamine, or placebo + placebo.
The trial was begun on 12/30/20, completed on 1/28/22 and registered with ClinicalTrials.gov: the designated trial # is NCT04510194.
Number of participants
Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned to the protocol, as outlined above. People who were already taking one of the study medications or who had already received a COVID-19 treatment were excluded. 1126 patients consented to long-term follow-up and completed at least one follow-up session, at 6 months. Of the 1126 long-term participants, 1074 (95%) completed a nine-month follow-up. Of these, 632 were female (44 were pregnant and therefore, were not assigned to the fluvoxamine or ivermectin groups). 494 were male. All were assessed for Long Covid by day 300: Overall, 93 (8·3%) of 1126 participants were diagnosed with long COVID by day 300.
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Mister T needs testosterone, for all his functions
Testosterone is called the “male sex hormone” and is much higher in men, but it is important to both genders: everyone needs it, to support muscle, the heart, personality, self-confidence and libido.
In youth, Testosterone is mainly made in the testicles (or ovaries); but in fact, all our cells convert DHEA into TESTOSTERONE, for their own use.
DHEATESTOSTERONE
This conversion was termed “intracrinology” by Professor Fernand Labrie, [1], of Laval University, in Quebec.
Actions of Testosterone
Testosterone subserves maintenance and repair of muscle (the heart included), bone, skin, sweat glands and hair. It supports the libido in both males and females, maintaining self-confidence, minimising our anxieties and shielding us from depression.
Maximum testosterone production, approximately 10 times more in males than in females, begins at puberty. In boys, it is responsible for development of the male sex chacteristics; beard and body hair, deepening of the voice by enlargement of the larynx, Increased muscle mass, stronger, heavier bones, heightened self-confidence and development of the prostate and the penis. In girls, testosterone production is insufficient to stimulate male pattern hair growth, hypertrophy of the larynx and other male characteristics; but it is important nevertheless, because it supports self-confidence, self-assurance, cognition and libido.
Male testosterone levels
Serum Testosterone remains high through the third decade, but a gradual fall in production, approximately 1% per year, starts at age 26 in both sexes. In women, the normal serum testosterone at age 20–25 is only 20-30 picomoles per litre, so a 1% loss per annum is easily demonstrated. However a 1%/year downward trend in Testosterone is hard to “see” in men, because their normal blood level spans a wide range (60–900 pmol/litre) and because the male’s Testosterone level varies, both with the time of day (highest at 8AM) and with physical and sexual activity. Suffice it that although the testicles don’t lose function completely at “andropause”, as the ovaries do at menopause, by age 80 men’s testosterone production is 10-20% of what it was at 25.
Testosterone deficiency in the male
Testosterone deficiency is described below: note that the male testoterone level often doesn’t match with low testosterone symptoms: many older men with “low T” are fit, sexually active and cognitively sharp, while many men with mid-normal “T” present to the MD with Low-T problems, even in their 20s.
Female Testosterone levels
Mrs. T also needs testosterone: not too much, but it’s essential
Women’s ovaries shut down completely in menopause, ceasing to produce both estrogen and testosterone. The peripheral cells continue “intracrine” testosterone production, but the amount made depends on the DHEA supply, so very little gets into the blood. Therefore In post-menopausal women, serum Testosterone tends towards zero, with reduced self-confidence and minimised libido.
Female Low Testosterone Syndrome
In contrast to the male’s experience, reduced testosterone level in the female tends to be symptomatic, since it is always associated with DHEA deficiency and often, with Intracellular Hypothyroidism (IH).
The “low DHEA/testosterone syndrome” (my terminology) in the female usually begins between age 26 and 30, but can at times be seen by age 20. It often presents with hypothyroid symptoms: hair loss, brittle fingernails, dry skin, vaginal dryness, reduced self-confidence, low libido, “fuzzy thinking”, poor glucose and cholesterol management, weight gain, etc.
The syndrome usually responds quickly and well, to oral supplementation of DHEA. However whether it responds to DHEA or not, thyroid tests, including TSH, FT4, FT3, T3 and Reverse T3, should be done, so as to diagnose or exclude IH, which is easily and safely treated with slow-release Triiodothyronine.
Childhood PTSD and Testosterone deficiency
Childhood PTSD from physical, mental or sexual abuse, often unrecognised, results in prolonged hypercortisolemia (Increased cortisol), and reduced DHEA, production. Cortisol suppresses T4 conversion into T3, so the net result is combined intracellular hypothyroidism and DHEA/testosterone deficiency in the teen years. Along with low DHEA, Testosterone, Progesterone and Allopregnanolone are also suppressed, further compounding the hypothyroidism.
Thus childhood PTSD sets the stage for DHEA/testosterone/deficiency, plus Intracellular Hypothyroidism and/or Progesterone/Allopregnanolone deficiency in the “20s” and severe, symptomatic deficiency by the “30s”. To my mind this is a significant background reason for depression and obesity in the “troubled teen” and the young adult.
Obviously, children caught in these circumstances should have a full thyroid hormone panel of tests, to diagnose and treat the Low T3 Syndrome if it is present.
CAVEATS
There need not have been a frank episode of PTSD: chronic neglect, or the subjective perception of inequity and unfairness in the family dynamic, is sufficient to Induce the Hypercortisolism, which leads to the Low T3 Syndrome, in the child.
The best measure of Testosterone-maufacturing capability in the female, is to check the DHEA level: DHEA is the precursor of “T”, so its level gives an accurate measure of The individual’s capacity for T production. DHEA peaks a little earlier in the morning than testosterone does, but it doesn’t rise and fall with exercise and/or sex, as testosterone does. Therefore “what you see, is what she’s got”.
The peripheral cells have a family of 30 (or so) enzymes, which the cell employees, to convert DHEA into its own mix of “microhormones”. Each cell type employs its own selection of enzymes to “mix and match” an individual hormone cocktail for its day-to-day activities and its internal maintenance and repair.
As the DHEA supply falls, all cells begin to suffer from DHEA deficiency, but some cell types are more sensitive to “DHEA starvation” than others, so the visible and symptomatic effects vary from person to person.
Surveillance and management
For “best practice” all patients should, at the time of admission to a family practice, routinely be investigated with a “thyroid profile“, including TSH, free T4, free T3 and reverse T3.” The thyroid profile should be repeated yearly and ad hoc: in particular, women presenting with hair loss, brittle fingernails, infertility, recurrent spontaneous abortion and other symptoms reminiscent of hypothyroidism, should be referred for thyroid testing.
If this were done, with diagnosis and correction of IH as necessary, (1), affected individuals would be relieved of the loss of self-image, poor sleep and low-grade depression which reduces the quality of life of so many young women and (2), the frequency of visits to the family doctor would decline and the net cost of our medical system would be reduced.
EVERYBODY is in the game !
We all, males and females, need, make and use Testosterone, and sooner or later we all become Testosterone deficient. So we all develop some symptoms and/or signs of low testosterone eventually. The Baltimore Longitudinal Study of Aging deems the incidence of hypogonadism * to be 20% in men over 60, 30% in men over 70 and 50% in men over 80 years of age (that may be a little optimistic!).
* I hate the term “Hypogonadism”: the problem is low testosterone, not low gonads !
The symptoms are mixed, due to Cortisol’s suppression of DHEA, Testosterone, Progesterone, Allopregnanolone, Thyroid 3 and sometimes, Estrogens. Also, our hormones go down with age, so single-hormone deficiency is rare.
(2) High-grade problems: Anaemia Reduced bone mass and increased bone fragility Reduced muscle mass Heart “events”: sometimes, heart failure Obesity, with or without cholesterol and glucose management aberrations Cognitive decline Various syndromes, diseases and illnesses, most of which are “DHEA-responsive”, can be considered to be reactions of tissues sensitive to Testosterone deficiency, (or) reduction of Testosterone availability, below their threshold of need.
Testosterone replacement Therapy
Men
Testosterone replacement therapy (TRT) for men with symptomatic deficiency has benefits, such as increased libido and energy level, improved bone density, Increased red blood cell production, increased muscle strength and cardioprotective effects: this is well documented.
Women
TRT does precisely the same for women, but testosterone’s awkward delivery problems (destruction of orally delivered testosterone by the liver, the liability to transmission of testosterone creams to sexual partners or children and the “spike and crash” problems associated with injectables) renders testosterone unsatisfactory for treating them.
DHEA is preferable: in the female, oral DHEA translates within hours, into increased serum testosterone and the serum DHEA elevation is of no metabolic consequence. The dosage of oral DHEA can therefore be monitored with serial estimations of serum testosterone.
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