Scoliosis (even in females) may be driven by low androgen levels, DHT may treat it

[haidut]

I am posting about this condition as it seems recently its numbers have absolutely exploded in the general population. Scoliosis used to be a relatively uncommon condition, usually present in adults over the age of 50. Mainstream medicine has no explanation for its possible causes, but suspects inflammation is involved. The study below suggests that a deficiency specifically of DHT, known to occur in all aging adults, may be the primary cause. Conversely, administration of DHT may be able to treat/reverse it. While this study did not directly address the topic, several other studies have demonstrated that chronic exposure to glucocorticoids (whether from stress or with synthetic ones by prescription) can reliable cause this pathology, and estrogen can as well. Thus, scoliosis seems little more than another biomarker of stress/aging and as such, its alarming increase in young adults and kids is a testament to the deteriorating environment in which we live.

Lower androgen levels promote abnormal cartilage development in female patients with adolescent idiopathic scoliosis - PubMed
"...Previous studies have confirmed that androgen can promote cortical bone formation through IL-6, which indicated that androgen plays a very important regulatory role in bone formation and growth (17). A study conducted by ElBaradie et al. demonstrated that DHT regulates growth plate chondrocytes in a sex-specific manner via rapid signaling pathways (34). In an earlier study, Raz et al. found that rat costochondral growth plate chondrocytes exhibit sex-specific and cell maturation-dependent responses to testosterone. In addition, these researchers proposed that the specific response of chondrocytes to hormones requires further metabolism of testosterone to DHT (35). Therefore, in our study, primary chondrocytes from AIS patients were treated with 5×10−7 M DHT, and the results showed that androgen played an important role in cartilage through IL-6. Specifically, DHT inhibited IL-6 expression through AR activation in chondrocytes of AIS patients. In addition, the serum androgen levels in patients with AIS were lower than those in the non-AIS group, which resulted in a weakened inhibitory function of androgen on IL-6 in patients with AIS. These results suggest that androgen might play a protective role in the development of AIS to inhibit IL-6-induced abnormal chondrocyte development. In conclusion, this study provides a new perspective for studying the pathogenesis of AIS. Our results show that androgen can reduce abnormal cartilage development in patients with AIS through AR/IL-6/STAT3 pathway inhibition (Figure 7). The data suggest that decreased androgen levels in female AIS patients might play a potential role in the occurrence of AIS."

 

[Peatness]

@haidut do you know if a drug like telmisartan contributes to lowered androgen in women without polycystic ovary syndrome.

Decreased androgen levels and improved menstrual pattern after angiotensin II receptor antagonist telmisartan treatment in four hypertensive patients with polycystic ovary syndrome: case series - PubMed

We describe 4 consecutive hypertensive women with polycystic ovary syndrome, classified according to the National Institute of Child Health and Human Development (NICHD) criteria, treated with telmisartan 40 mg/d for six months. Blood pressure, menstrual pattern, body mass index (BMI)...

pubmed.ncbi.nlm.nih.gov

What is the recommended way for a women to raise androgens without running the risk of it converting to estrogen?

 

[Cameron]

Maybe another reason to use androsterone naval route! Could 1 mg androsterone be enough through the naval to long term increase dht and 5 ar expression? Topical elsewhere on the body doesn’t seem to absorb as effectively and oral seems hit or miss @haidut

 

[Cameron]

@haidut do you know if a drug like telmisartan contributes to lowered androgen in women without polycystic ovary syndrome.

Decreased androgen levels and improved menstrual pattern after angiotensin II receptor antagonist telmisartan treatment in four hypertensive patients with polycystic ovary syndrome: case series - PubMed

We describe 4 consecutive hypertensive women with polycystic ovary syndrome, classified according to the National Institute of Child Health and Human Development (NICHD) criteria, treated with telmisartan 40 mg/d for six months. Blood pressure, menstrual pattern, body mass index (BMI)...

pubmed.ncbi.nlm.nih.gov

What is the recommended way for a women to raise androgens without running the risk of it converting to estrogen?

Dhea topically in women seems to primarily convert to androgens and less into estrogen than in males as seen in the current literature. Maybe a little androsterone as it is an antagonist to estrogen and downstream converts to the 5alpha reduced androgen dht and weaker metabolites

 

[Peatness]

Dhea topically in women seems to primarily convert to androgens and less into estrogen than in males as seen in the current literature. Maybe a little androsterone as it is an antagonist to estrogen and downstream converts to the 5alpha reduced androgen dht and weaker metabolites

Cheers.. I've got both dhea and androsterone I just need to start using them - properly.

Just found this article

"while supplementing DHT in women is possible and apparently greatly improves body composition, it may have undesirable virilizing effects in some women due to its high androgenic potency. Progesterone, aspirin, vitamin E, and DHEA (a good DHT precursor in women) are probably some of the most widely available and cost-effective options with less risk for virilizing side effects."

Estrogens cause obesity / PCOS in women, DHT is protective – To Extract Knowledge from Matter

I still need to know what effect telmisartan is having on my hormones - I've not been right since starting it

 

[Cameron]

Cheers.. I've got both dhea and androsterone I just need to start using them - properly.

Just found this article

"while supplementing DHT in women is possible and apparently greatly improves body composition, it may have undesirable virilizing effects in some women due to its high androgenic potency. Progesterone, aspirin, vitamin E, and DHEA (a good DHT precursor in women) are probably some of the most widely available and cost-effective options with less risk for virilizing side effects."

Estrogens cause obesity / PCOS in women, DHT is protective – To Extract Knowledge from Matter

I still need to know what effect telmisartan is having on my hormones - I've not been right since starting it

Creatine and lifting weights for women would also be useful. I think the things women fear will make them manly actually has the opposite impact. Of course we don’t want super physiological amounts of androgens in females but certainly the common birth control high stress high estrogen low androgen modern female is not a physically or mentally healthy individual.

 

[aliml]

IL-6 levels are increased in nearly all disease states [1].

It decreases Treg cells, which in turn blocks our ability to create tolerance for proteins we ingest – causing allergies [12]. It also increases the production of neutrophils, which is inflammatory [2].

Interleukin-6 is a decent predictor of cognitive decline in late midlife. A 10-year decline in reasoning was greater among people with high IL-6 than those with low IL-6. In addition, people with high IL-6 had 1.81 times greater odds of a decline in a test that measures normal cognitive function [13].

IL-6 may cause feelings of “hopelessness“. This state strongly correlated with IL-6 levels [14] and we know this cytokine can cause brain changes that lead to a worsened mood. IL-6 is also correlated with violent suicide, impulsivity, and monotony avoidance [15].

IL-6 causes elevated blood sugar levels, which we know is problematic for general health [16].

IL-6 levels are higher in people with IBS [17, 18].

Studies have found that IL-6 aggravates the effects of stress hormones (CRH) on our gut mucosa, which causes IBS [19]. It also causes IBS by activating gut neurons [20], which alters peristalsis. IL-6 can cause leaky gut [21].

IL-6 may lessen fatigue by stimulating the HPA axis and suppressing TNF-alpha (thereby increasing orexin). Specifically, it stimulates the release of the corticotrophin-releasing hormone (CRH) by the hypothalamus (reversed by a COX inhibitor) [22].

It increases nitric oxide [4], which can be good or bad, depending on the situation.

At higher levels, IL-6 increased the release of vasopressin and oxytocin [22], which acts to decrease urination, among other effects.

IL-6 suppresses or ‘hypermethylates‘ gene expression in the brain, which leads to a variety of problems [2].

For example, it decreases BDNF, a brain growth factor, which is how it contributes to depression [2].

People with major depressive disorder have elevated IL-6 (TNF-alpha) [23] and it likely contributes to a worse mood overall.

It can also lead to lower testosterone levels [24].

IL-6 also decreases performance by decreasing the conversion of T4 to T3 (thyroid hormones), resulting in lower levels of T3. This occurs as a result of IL-6 causing oxidative stress and lowering glutathione levels [26, 27].

IL-6 contributes to schizophrenia by inhibiting (or hypermethylation) a gene (GAD67) that is important for GABA to work properly [2].

HDAC inhibitors are beneficial for cognitive disorders because they increase gene expression for growth factors like BDNF. IL-6 does the opposite by increasing HDAC [28]. Resistant starch is a powerful way to inhibit HDAC and therefore increase BDNF.

IL-6 is the most potent inducer of CRP, an inflammatory marker, but as I will explain below, you can have normal CRP levels and abnormal IL-6 levels.

It can create and worsen food sensitivities and autoimmune issues by increasing IgG and IgM antibodies [29]. Testosterone decreases these antibodies, but IL-6 is capable of increasing them even with high levels of testosterone [29]. (Estrogen increases these antibodies) [30].

IL-6 can also cause skin problems. When your natural skin fungus gets out of control the body attacks it with cytokines that include IL-6 (also IL-1b, TNF, IL-8), which recruits other aspects of the immune system [31]. IL-6 is elevated in people with tinea versicolor, a skin fungus [32]. IL-6 also increases Th22 cells, which disrupts skin microbial balance [33].

IL-6 (or IL-21 according to some) can increase Th17 cells, which are pro-inflammatory. To do this, you also need elevated TGF-β [34].

Diseases Associated With Interleukin-6​

• Heart disease [47]
• Cancer (Myeloma [28], Prostate [28], Breast [48], etc…)
• Diabetes [28]
• Pain [49]
• Rheumatoid arthritis – strongest evidence [50], Fibromyalgia [51], Multiple Sclerosis [52], Behcet’s [53], SLE [54], System Sclerosis [46].
• Asthma. IL-6 promotes Th2 activation and allergic responses and inhibits the activity of regulatory T cells (Tregs), which helps get rid of substances you’re allergic to.
• IBS [18], IBD, Crohn’s [46]
• Major depression [55], Bipolar [55], Schizophrenia [55], Alzheimer’s [28], Intellectual disability [56]
• Osteoporosis (postmenopausal) [57]. IL-6 promotes osteoclasts, which degrade bones [2].
• PCOS [58]
• Others: Diabetic neuropathy [59], Chemotherapy-induced neuropathy [60], Tinea versicolor, a skin fungus [32], Carpal Tunnel Syndrome [61], Polymyalgia Rheumatica [62].

Top Ways to Inhibit IL-6​

• Spices: Bay leaves [63], Black pepper [63], Nutmeg [63], Oregano [63], Sage [63]
• Resistant starch [64]
• Zinc [65]
• Magnesium [66]
• Probiotics: B. infantis [67], S. boulardii [68], L. casei [69], L. Salivarius [70]
• Trehalose [71, 72]
• Jasmine Tea/EGCG[73]
• Vitamin D3 [74]
• PQQ [75]
• Andrographis/Andrographolide [76] – Out of 20 plants tested, Andrographis inhibited IL-6 the most and was more potent than dexamethasone. (IC50= .74mcg/ml)
• Black Cumin Seed Oil/Thymoquinone [77]
• Curcumin [78, 79]
• Licorice [80]
• Fish oil/DHA [81]
• Fisetin [82]
• Cinnamon [63] /Sodium Benzoate
• Molecular hydrogen machine [83]
• Aspirin [84]
• Boswellia [85]
• Lithium[86]
• Hydroxytyrosol [87]
• Apigenin [63]
• Luteolin [88]
• Quercetin [63]
• Resveratrol (500 mg, with 5 g leucine) [79, 89]
• Red Yeast Rice/Lovastatin [90]

Inhibiting Interleukin-6 (IL-6): The Key To Health - SelfHack

Interleukin-6 (IL-6) is increased in almost all disease states. Read on to discover the causes of high IL-6 and natural hacks to decrease it.

selfhack.com

 

[Cameron]

IL-6 levels are increased in nearly all disease states [1].

It decreases Treg cells, which in turn blocks our ability to create tolerance for proteins we ingest – causing allergies [12]. It also increases the production of neutrophils, which is inflammatory [2].

Interleukin-6 is a decent predictor of cognitive decline in late midlife. A 10-year decline in reasoning was greater among people with high IL-6 than those with low IL-6. In addition, people with high IL-6 had 1.81 times greater odds of a decline in a test that measures normal cognitive function [13].

IL-6 may cause feelings of “hopelessness“. This state strongly correlated with IL-6 levels [14] and we know this cytokine can cause brain changes that lead to a worsened mood. IL-6 is also correlated with violent suicide, impulsivity, and monotony avoidance [15].

IL-6 causes elevated blood sugar levels, which we know is problematic for general health [16].

IL-6 levels are higher in people with IBS [17, 18].

Studies have found that IL-6 aggravates the effects of stress hormones (CRH) on our gut mucosa, which causes IBS [19]. It also causes IBS by activating gut neurons [20], which alters peristalsis. IL-6 can cause leaky gut [21].

IL-6 may lessen fatigue by stimulating the HPA axis and suppressing TNF-alpha (thereby increasing orexin). Specifically, it stimulates the release of the corticotrophin-releasing hormone (CRH) by the hypothalamus (reversed by a COX inhibitor) [22].

It increases nitric oxide [4], which can be good or bad, depending on the situation.

At higher levels, IL-6 increased the release of vasopressin and oxytocin [22], which acts to decrease urination, among other effects.

IL-6 suppresses or ‘hypermethylates‘ gene expression in the brain, which leads to a variety of problems [2].

For example, it decreases BDNF, a brain growth factor, which is how it contributes to depression [2].

People with major depressive disorder have elevated IL-6 (TNF-alpha) [23] and it likely contributes to a worse mood overall.

It can also lead to lower testosterone levels [24].

IL-6 also decreases performance by decreasing the conversion of T4 to T3 (thyroid hormones), resulting in lower levels of T3. This occurs as a result of IL-6 causing oxidative stress and lowering glutathione levels [26, 27].

IL-6 contributes to schizophrenia by inhibiting (or hypermethylation) a gene (GAD67) that is important for GABA to work properly [2].

HDAC inhibitors are beneficial for cognitive disorders because they increase gene expression for growth factors like BDNF. IL-6 does the opposite by increasing HDAC [28]. Resistant starch is a powerful way to inhibit HDAC and therefore increase BDNF.

IL-6 is the most potent inducer of CRP, an inflammatory marker, but as I will explain below, you can have normal CRP levels and abnormal IL-6 levels.

It can create and worsen food sensitivities and autoimmune issues by increasing IgG and IgM antibodies [29]. Testosterone decreases these antibodies, but IL-6 is capable of increasing them even with high levels of testosterone [29]. (Estrogen increases these antibodies) [30].

IL-6 can also cause skin problems. When your natural skin fungus gets out of control the body attacks it with cytokines that include IL-6 (also IL-1b, TNF, IL-8), which recruits other aspects of the immune system [31]. IL-6 is elevated in people with tinea versicolor, a skin fungus [32]. IL-6 also increases Th22 cells, which disrupts skin microbial balance [33].

IL-6 (or IL-21 according to some) can increase Th17 cells, which are pro-inflammatory. To do this, you also need elevated TGF-β [34].

Diseases Associated With Interleukin-6​

• Heart disease [47]
• Cancer (Myeloma [28], Prostate [28], Breast [48], etc…)
• Diabetes [28]
• Pain [49]
• Rheumatoid arthritis – strongest evidence [50], Fibromyalgia [51], Multiple Sclerosis [52], Behcet’s [53], SLE [54], System Sclerosis [46].
• Asthma. IL-6 promotes Th2 activation and allergic responses and inhibits the activity of regulatory T cells (Tregs), which helps get rid of substances you’re allergic to.
• IBS [18], IBD, Crohn’s [46]
• Major depression [55], Bipolar [55], Schizophrenia [55], Alzheimer’s [28], Intellectual disability [56]
• Osteoporosis (postmenopausal) [57]. IL-6 promotes osteoclasts, which degrade bones [2].
• PCOS [58]
• Others: Diabetic neuropathy [59], Chemotherapy-induced neuropathy [60], Tinea versicolor, a skin fungus [32], Carpal Tunnel Syndrome [61], Polymyalgia Rheumatica [62].

Top Ways to Inhibit IL-6​

• Spices: Bay leaves [63], Black pepper [63], Nutmeg [63], Oregano [63], Sage [63]
• Resistant starch [64]
• Zinc [65]
• Magnesium [66]
• Probiotics: B. infantis [67], S. boulardii [68], L. casei [69], L. Salivarius [70]
• Trehalose [71, 72]
• Jasmine Tea/EGCG[73]
• Vitamin D3 [74]
• PQQ [75]
• Andrographis/Andrographolide [76] – Out of 20 plants tested, Andrographis inhibited IL-6 the most and was more potent than dexamethasone. (IC50= .74mcg/ml)
• Black Cumin Seed Oil/Thymoquinone [77]
• Curcumin [78, 79]
• Licorice [80]
• Fish oil/DHA [81]
• Fisetin [82]
• Cinnamon [63] /Sodium Benzoate
• Molecular hydrogen machine [83]
• Aspirin [84]
• Boswellia [85]
• Lithium[86]
• Hydroxytyrosol [87]
• Apigenin [63]
• Luteolin [88]
• Quercetin [63]
• Resveratrol (500 mg, with 5 g leucine) [79, 89]
• Red Yeast Rice/Lovastatin [90]

Inhibiting Interleukin-6 (IL-6): The Key To Health - SelfHack

Interleukin-6 (IL-6) is increased in almost all disease states. Read on to discover the causes of high IL-6 and natural hacks to decrease it.

selfhack.com

TSH and IL-6

Thyroid-Stimulating Hormone Induces Interleukin-6 Release from Human Adipocytes through Activation of the Nuclear Factor-κB Pathway

Our objective was to identify the signaling pathway activated by TSH that induces IL-6 secretion from human abdominal sc differentiated adipocytes. Human a

academic.oup.com

Thyroid-Stimulating Hormone Induces Interleukin-6 Release from Human Adipocytes through Activation of the Nuclear Factor-?B Pathway
Tayze T. Antunes, AnneMarie Gagnon, Melanie L. Langille, and Alexander Sorisky
Departments of Medicine and Biochemistry, Microbiology, and Immunology, University of Ottawa, Chronic Disease Program, Ottawa Health Research Institute, Ottawa, Canada K1Y 4E9
Our objective was to identify the signaling pathway activated by TSH that induces IL-6 secretion from human abdominal sc differentiated adipocytes. Human abdominal sc preadipo- cytes in culture were differentiated into adipocytes. IL-6 re- lease stimulated by TSH was inhibited by 35% (P < 0.05) with SN50, an inhibitor of nuclear factor-?B (NF-?B) nuclear trans- location, and 60% (P < 0.01) with sc-514, an inhibitor of inhib- itory-?B (I?B) kinase (IKK)-?. Phosphorylation of IKK? in- creased upon TSH treatment (10.3-fold, P < 0.01), and I?B? levels were reduced by 78% (P < 0.01). TSH activated NF-?B (23-fold, P < 0.001), a process that was inhibited (60%, P < 0.01)
IN ADDITION TO energy storage and release, adipose tissue releases a variety of cytokines (adipokines) with wide-rang- ing physiological effects, including appetite, energy expendi- ture, insulin sensitivity, and coagulation. Deregulation of adi- pokine production is associated with a proinflammatory, proatherogenic state. Adipose tissue constitutes a significant source of circulating IL-6 (1). IL-6 has been identified as an independent risk factor for cardiovascular disease. A recent systematic review confirmed that serum IL-6 levels predict the development of cardiovascular disease (CVD) with an adjusted relative risk between 1.1 and 3.1 (2). Studies published subse- quently continue to demonstrate IL-6 is a significant prognostic indicator of CVD (3–5). However, our understanding of hor- monal regulators of adipocyte production of IL-6 is incomplete.
In subclinical hypothyroidism, TSH levels rise to compensate for mild thyroid gland failure and thereby maintain thyroid hormone levels in the normal range. However, a higher risk for CVD appears to be independently associated with subclinical hypothyroidism. A recent metaanalysis concluded that sub- clinical hypothyroidism is associated with an elevated risk of CVD in observational studies (odds ratio 1.65, 95% confidence interval 1.28–2.12), with a similar trend noted in prospective studies (odds ratio 1.42, 95% confidence interval 0.91–2.21) (6). Furthermore, acute administration of TSH to biochemically eu- thyroid patients (healthy thyroid cancer patients on l-thyroxine
First Published Online February 28, 2008
Abbreviations: CHO, Chinese hamster ovarian; CREB, cAMP re- sponse element-binding protein; CVD, cardiovascular disease; FBS, fetal bovine serum; GPCR, G protein-coupled receptor; I?B, inhibitory-?B; kinase; IKK, inhibitor of I?B kinase; NF-?B, nuclear factor-?B; PKA, protein kinase A; RT, reverse transcriptase; TSHR, TSH receptor.
Endocrinology is published monthly by The Endocrine Society (http:// www.endo-society.org), the foremost professional society serving the endocrine community.
by SN50. Inhibition of protein kinase A by H89 did not affect TSH-stimulated IKK? phosphorylation or I?B? degradation. TSH-mediated NF-?B activation and IL-6 induction also spe- cifically occurred in Chinese hamster ovarian cells expressing the human TSH receptor, resulting in a 5.9-fold (P < 0.001) increase in IKK? phosphorylation and a 9.5-fold increase in IL-6 mRNA expression. Our data demonstrate that the IKK?/ NF-?B pathway is a novel TSH target that is required for TSH-induced IL-6 release from human adipocytes. (Endocri- nology 149: 3062–3066, 2008)

 

[Peatness]

Creatine and lifting weights for women would also be useful. I think the things women fear will make them manly actually has the opposite impact. Of course we don’t want super physiological amounts of androgens in females but certainly the common birth control high stress high estrogen low androgen modern female is not a physically or mentally healthy individual.

In a world were 'trans' has become a common insult for women is it a surprise that women don't want to pump weights? I personally don't buy into that way of thinking but I bet a lot of young women do. Everything has it's price. Supplementing creatine is not a good idea for most people and certainly not for me. A recently blood test showed this was elevated.

If anyone has experience with telmisartan please let me know your thoughts

 

[YourUniverse]

I wonder if people having trouble with their fascia (myself included) have something like this going on. Trying to tag @rei for comment. Best non-DHT options? Aspirin, vitamin E? Weight lifting and creatine?

 

[Peatness]

Mast cell disorders in Ehlers-Danlos syndrome

Interleukin-6 and mast cells - PubMed

Interleukin (IL) 6 is a pleiotropic cytokine (26 kDa) that originally was named interferon beta 2 or B cell-stimulating factor or differentiating B cell factor inducing immunoglobulin production. IL-6 is produced in many diseases. After secretion, IL-6 binds to its receptor IL-6R alpha (gp 80)...

pubmed.ncbi.nlm.nih.gov

Mast cell disorders in Ehlers-Danlos syndrome - PubMed

Well known for their role in allergic disorders, mast cells (MCs) play a key role in homeostatic mechanisms and surveillance, recognizing and responding to different pathogens, and tissue injury, with an array of chemical mediators. After being recruited to connective tissues, resident MCs...

pubmed.ncbi.nlm.nih.gov

 

[Gustav3Y]

Any moment of the day is a good moment to test serum IL-6 levels?
For the last 12 months I keep thinking of doing an IL-6 test.
Ironically I have a plethora of health issues but CRP always very low.

 

[Dr. B]

In a world were 'trans' has become a common insult for women is it a surprise that women don't want to pump weights? I personally don't buy into that way of thinking but I bet a lot of young women do. Everything has it's price. Supplementing creatine is not a good idea for most people and certainly not for me. A recently blood test showed this was elevated.

If anyone has experience with telmisartan please let me know your thoughts

why not a good idea for most people? it increases choline, methionine, arginine etc?

 

[I'm.No.One]

Just to share my son (18) suddenly developed scoliosis after severe atypical SIBO that led to extreme malnutrition (it was 1.5 years of chronic vomiting/40+ lbs weight lost).

(Which he got from killing his gut bacteria with eating the spiciest food possible with his grandfather ?)

While he's recoverd from the SIBO (that I figured out & treated) he's now at the age of 18 living with chronic back pain.

We do physical therapy/home exercises for it, but he's done growing (bones are fully fused) so this won't correct anything.

I'm curious if anyone can make recommendations on sources of DHT?

Thinking I'd like to try to combine it with the physical therapy to see if there are any positive changes. It's not a super drastic curve so any amount of potential improvement would likely give him relief.

Also, just to say, I know he didn't have scoliosis growing up. When he was much younger he had a pretty serious bone cyst in his arm (common, most kids outgrow them, he broke his arm is how we found out) so attention has been paid to all of his bones until 15 so it would have been seen.

Anyone have any thoughts on this matter?