OK We So Know Prostaglandin D2 Is The Main Driver Behind Baldness. What Can We Do About It?

[YourUniverse]

Since the steroids in milk are identical to ours, you might expect the body to downregulate production of the corresponding endogenous steroids. I think this would would work for the ones having a strong negative‐feedback control, but this control obviously fails when it comes to the androstenedione—which can cause acne. This doesn't happen in everybody, and would of course depend on the dose and circulating levels of sex hormone binding globulin (SHBG). But since goat milk has a fatty acid profile only equaled by that of coconut, beef, and chocolate, it could be worth consuming despite the steroids it contains (and it has a high mineral content besides). I used to eat about ¹⁄₂ # per day of either goat or cow cheese, and I think you'd be able to tell the difference if you pay attention.

If I had to make the choice, I'd take the non‐organic goat milk.

What do you think about aspirin in conjunction with hair recovery efforts?

 

[nbznj]

True that DHT is a much more characteristic male hormone. Take DHT-based steroids (besides oxymetholone): their hardening, leaning effects are obvious. I never really thought of this before.

 

[Travis]

What do you think about aspirin in conjunction with hair recovery efforts?

Well, it's a good cyclooxgenase inhibitor yet is water‐soluble: Oleuropein and oleocanthal are good lipid‐soluble cyclooxgenase inhibitors.

But this water‐solubility of aspirin, its small‐molecule nature, and it's track record mean that it can be taken internally in large amounts—more‐or‐less safely. But of course, the less linoleic acid we consume the less need we have for cyclooxgenase inhibitors; aspirin dosing could be directly dependent on current and prior ω−6 intake, which largely determines the amount of arachidonic acid on the cell membrane. Although the cyclooxgenase enzyme will transform other lipids, none of them are as pathological as the 1‐ and 2‐series prostaglandins derived from ω−6 fatty acids. Cyclooxgenase working on eicosapentaenoic acid will form the less active 3‐series prostaglandins, and when Mead Acid becomes the substrate the product is a simple acyclic hydroxylated eicosanoid somewhat similar to a leukotriene.

I think the main source of ω−6 on this forum is eggs since most people here avoid nuts, grains, pork, and dark chicken. It would seem that the more linoleic acid one consumes, the more aspirin they'd need to take to counter the increased 1‐ and 2‐series prostaglandin formation.

 

[nbznj]

dismiss

 

[nbznj]

some food for thought - I've always seen better hair when I'm taking nolvadex/tamoxifen which may have happened when I'd be going higher than my standard TRT dose :) This drug is an antagonist to the scalp ERbeta, agonist/antagonist to the ERalpha, causes alopecia in females... good for males? Also does it lower prolactine? I've read conflicting reports between rodents and humans

Dr. Gabe Mirkin on Health, Fitness and Nutrition. | NEW BREAKTHROUGHS IN MALE PATTERN BALDNESS

@Joeyd regarding AIs and progesterone receptors... something worth reading:

J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9.

Aromatase inhibitors: cellular and molecular effects.

Miller WR, Anderson TJ, White S, Larionov A, Murray J, Evans D, Krause A, Dixon JM.

Breast Unit, Western General Hospital, Edinburgh, Scotland, UK. [email protected]

Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in histological grading may also take place, most notably a reduction in mitotic figures. This probably reflects an influence on proliferation as most tumours (82%) show a marked decrease in the proliferation marker, Ki67. These effects are generally more dramatic than seen with tamoxifen given in the same setting. Differences between aromatase inhibitors and tamoxifen are also apparent in changes in steroid hormone expression. Thus, immuno-staining for progesterone receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming undetectable in many. This contrasts with effects of tamoxifen in which the most common change on PgR is to increase expression. Changes in proliferation occur rapidly following the onset of exposure to aromatase inhibitors. Thus, neoadjuvant studies with letrozole in which tumour was sampled before and after 14 days and 3 months treatment show that decreased expression of Ki67 occur at 14 days and, in many cases, the effect is greater at 14 days than 3 months. These early changes precede evidence of clinical response but do not predict for it. However, this study design has allowed RNA analysis of sequential biopsies taken during the neoadjuvant therapy. Based on clustering techniques, it has been possible to subdivide tumours into groups showing distinct patterns of molecular changes. These changes in tumour gene expression may allow definition of tumour cohorts with differing sensitivity to aromatase inhibitors and permit early recognition of response and resistance.

AIs seem to lower progesterone pretty bad. Bodybuilders from the 50s were using Nolvadex as an AI... which is ridiculed now. Look at their hair though. Conversely they were abusing deca-durabolin so progesterone related side effects were common.


For people who do not want to use Nolvadex, look at this thread... Vitamin E it is:

Vitamin E Is An Estrogen Receptor Antagonist

 

[Travis]

So‐called 'androgenic' alopecia is less prevalent in Korea, by quite a bit:

But this cannot be 'androgenic,' because many Koreans have a 'female hair loss pattern.' This is characterized by the retention of hair curcumscribing the hairline, 360°, with only diffuse crown thinning.

'In Korean men, the prevalence of AGA (Norwood III or above) at all ages was 14.1%. It increased steadily with advancing age, but was lower than that of caucasians: 2.3% in the third decade, 4.0% in the fourth decade, 10.8% in the fifth decade, 24.5% in the sixth decade, 34.3% in the seventh decade and 46.9% over 70 years. Type III vertex involvement was the most common type in the third decade to the seventh decade; over 70 years, type VI was most common. A `female pattern' was observed in 11.1% of cases. In Korean women, the prevalence of AGA (Ludwig I or above) [?] at all ages was 5.6%. It also increased steadily with advancing age: 0.2% in the third decade, 2.3% in the fourth decade, 3.8% in the fifth decade, 7.4% in the sixth decade, 11.7% in the seventh decade and 24.7% over 70 years.' ―Paik​

So not only do Koreans have less hair loss, what they do lose is lost in a way similar to females. I think this makes sense if you think about their ω−6/ω−3 ratios and perhaps relative lack of stress. Nonetheless, Koreans aren't perfect and still consume linoleic acid and some no doubt have stressful lives (think Fukushima; fish prices; ect.).

The authors attempt to explain this, of course, by genetics; they do this in spite of absolutely no proof. While its' true that Asians' hair differs bit, perhaps having slight keratin polymorphisms (known to effect hair curl in animals), African Americans have similar hair and lose it to a greater extent. Also, many caucasians also have smooth black hair.

'However, analysis of candidate genes for AGA by restriction fragment length polymorphism found no genetic variation in the 5α-reductase type 1 gene or the 5α-reductase type 2 gene or their regulation.' ―Paik​

These types of studies of course totally demolish the idea that hair loss is dose-dependent on androgens. I have maintained that DHT only contributes to the extent that it acts on the thymus and the adrenals, two organs with a high-density of androgen receptors. For this reason, males have both a higher cortisol output on average and differential immune parameters (i.e. lower INF-γ). After all, it must work somewhere; dihydrotestosterone actually increases hair growth at the folliclle. The fact that DHT works circuitously through cytokines and cortisol also helps to explain why spironolactone and cyclosporine are more effective than finasteride.

I am willing to bet that Israeli men have the highest prevalence of alopecia simply on account the their extremely high ω−6/ω−3 ratio.

Paik, J‐H. "The prevalence and types of androgenetic alopecia in Korean men and women." British Journal of Dermatology (2001)​

 

[YourUniverse]

I think prolactin is more responsible for the female phenotype, and is more variable in males than estrogen. However: it is estrogen which transcribes for the prolactin receptor, and you need both ligand and receptor to get 'manboobs' and/or visceral fat. We all have some prolactin receptors in these areas, some more than others, so keeping prolactin down by avoiding exorphins—and perhaps also by taking bromocriptine or tyrosine—might seem wise for those striving to maintain a 100% natural male phenotype. I think everyone here avoid grains, but exorphins can also be found in soy—in addition to genestein—and cow's milk; however, goat and sheep milk much reduced (~10%) opiate potential due to a few substitutions in their casein isoform. Goat cheese and beef appear to be the best animal foods, since: they are very low in ω−6 fatty acids, they have largely non‐immunogenic peptides, and they are practically absent of prolactin‐stimulating exorphins.

What about whey protein? Does the extra processing have any effect on exorphins in cows milk?

 

[Hairfedup]

So‐called 'androgenic' alopecia is less prevalent in Korea, by quite a bit:

View attachment 8442

But this cannot be 'androgenic,' because many Koreans have a 'female hair loss pattern.' This is characterized by the retention of hair curcumscribing the hairline, 360°, with only diffuse crown thinning.

'In Korean men, the prevalence of AGA (Norwood III or above) at all ages was 14.1%. It increased steadily with advancing age, but was lower than that of caucasians: 2.3% in the third decade, 4.0% in the fourth decade, 10.8% in the fifth decade, 24.5% in the sixth decade, 34.3% in the seventh decade and 46.9% over 70 years. Type III vertex involvement was the most common type in the third decade to the seventh decade; over 70 years, type VI was most common. A `female pattern' was observed in 11.1% of cases. In Korean women, the prevalence of AGA (Ludwig I or above) [?] at all ages was 5.6%. It also increased steadily with advancing age: 0.2% in the third decade, 2.3% in the fourth decade, 3.8% in the fifth decade, 7.4% in the sixth decade, 11.7% in the seventh decade and 24.7% over 70 years.' ―Paik​

So not only do Koreans have less hair loss, what they do lose is lost in a way similar to females. I think this makes sense if you think about their ω−6/ω−3 ratios and perhaps relative lack of stress. Nonetheless, Koreans aren't perfect and still consume linoleic acid and some no doubt have stressful lives (think Fukushima; fish prices; ect.).

The authors attempt to explain this, of course, by genetics; they do this in spite of absolutely no proof. While its' true that Asians' hair differs bit, perhaps having slight keratin polymorphisms (known to effect hair curl in animals), African Americans have similar hair and lose it to a greater extent. Also, many caucasians also have smooth black hair.

'However, analysis of candidate genes for AGA by restriction fragment length polymorphism found no genetic variation in the 5α-reductase type 1 gene or the 5α-reductase type 2 gene or their regulation.' ―Paik​

These types of studies of course totally demolish the idea that hair loss is dose-dependent on androgens. I have maintained that DHT only contributes to the extent that it acts on the thymus and the adrenals, two organs with a high-density of androgen receptors. For this reason, males have both a higher cortisol output on average and differential immune parameters (i.e. lower INF-γ). After all, it must work somewhere; dihydrotestosterone actually increases hair growth at the folliclle. The fact that DHT works circuitously through cytokines and cortisol also helps to explain why spironolactone and cyclosporine are more effective than finasteride.

I am willing to bet that Israeli men have the highest prevalence of alopecia simply on account the their extremely high ω−6/ω−3 ratio.

Paik, J‐H. "The prevalence and types of androgenetic alopecia in Korean men and women." British Journal of Dermatology (2001)​

So the androgen hypothesis is null? Everything you say makes sense but the balding community is stubbornly refusing to move away from androgenic issues as the source of baldness.

 

[Travis]

What about whey protein? Does the extra processing have any effect on exorphins in cows milk?

There is only one dairy exorphin, and it's buried in casein; so you wouldn't expect much exorphin in the whey fraction.

But this is an interesting speculation. I'm sure there's enough data out this. Bovine β-casomorphin has a high affinity to the μ‐receptor, and its binding has been shown to lower dopamine and increase prolactin. Perhaps the IGF-1 is released in response to prolactin? perhaps subsequent of the lowered dopaminergic flux to the pituitary as a result of β-casomorphin ingestion.. .

I had thought it could be Ca²⁺ that was releasing IGF-1 but after reading that IGF-1 is released primarily by the liver I started to think saturated fatty acids could be involved instead. This doesn't appear to be an endocrine hormone like insulin, prolactin, and growth hormone; insulin-like growth factor is produced by many tissues in a paracrine manner (i.e. TGF-β, VEGF).

Kaklamani, Virginia G. "Dietary fat and carbohydrates are independently associated with circulating insulin-like growth factor 1 and insulin-like growth factor–binding protein 3 concentrations in healthy adults." Journal of Clinical Oncology (1999)​

I am going to read this article and pull a few of the most pertinent quotes (as not to exhaust everyone's patience and to keep information density high.)

'INSULIN-LIKE GROWTH factor 1 (IGF-1) acts in an autocrine, paracrine, or endocrine manner to promote normal growth, induce malignant cellular proliferation, and regulate metabolism in an insulin-like manner.' ―Kaklamani

'In addition, acromegaly, a disorder characterized by elevated serum concentrations of IGF‐1, has been associated with elevated risk for developing colon cancer, whereas insulin‐like growth factor binding protein #3 (IGF₁BP#3), the major IGF₁‐binding protein in plasma, has been inversely and independently associated with the risk of breast and prostate cancer.' ―Kaklamani​

This quote highlights that bones have IGF‐1 receptors (osteoporosis, acromegaly) and also talks about IGF₁‐binding protein. If I remember correctly, this is transcriptionally upregulated by vitamin D—illustrating how this vitamin promotes differentiation over proliferation. Binding proteins aren't too rare in the body; for instance, interleukin-1 has a binding protein which inactivates it (a 'decoy receptor'). I am beginning to think that IGF₁ is more involved in protein synthesis and/or metabolic flux than calcium—which has its own peptide hormones. Perhaps an easy way to tell would be to see if it upregualtes phospholipase C.. .

'Red meat [methionine] and fat intake [not all fat, only ω−6 fatty acids] are positively associated with risk for malignancies, including prostate, colon, and, possibly, breast cancer.' ―Kaklamani

'It seems that red meat, as well as oils and fats, are positively associated with serum IGF-1 levels, whereas consumption of bread is negatively associated with serum IGF-1 levels.' ―Kaklamani
​

They haven't mentioned dairy yet, but the fact that wheat is negatively associated with IGF‐1 basically proves that the δ-opioid receptor is not involved.

'It seems that fat intake is positively associated with serum IGF-1 levels, whereas carbohydrate intake has a negative association.' ―Kaklamani​

Protein intake is not correlated, lipid intake is positively correlated, and carbohydrate intake is negatively correlated. I think the fact that protein is not correlated rules‐out the mTOR pathway in the liver and also the pituitary hormones, as these are controlled by dietary tryptophan (serotonin) and tyrosine (dopamine):

Further analysis reveals that saturated fatty acids increase IGF‐1 levels more than unsaturated fatty acids.

But there's a problem: The cell isn't thought to have 'saturated fatty acid receptors.' However: stearic acid is readily transformed into oleic acid in the liver by the action of Δ⁹‐desaturase, and oleic acid can bind bind to PPARα. If oleic acid is the stimulus than this would how both saturated fatty acids and unsaturated fatty acids are correlated.

But this doesn't make sense because bones don't need fatty acids, especially, and the sex hormone receptors are what seem most involved in transcribing both IGF-1 and it's cell membrane receptor (IGF‐1R): Della Torre, Sara. "Amino acid-dependent activation of liver estrogen receptor alpha integrates metabolic and reproductive functions via IGF-1." Cell metabolism (2011):

'With regard to the mechanism of liver ERα transcriptional activation by AA, previous reports demonstrated that ER directly regulated the IGF-I promoter (Gao et al., 2008, Hewitt et al., 2010).' ―Della Torre

'Our finding of a role of dietary amino acids in the control of reproduction in mammals is in line with previous reports showing that the deficiency of a single essential AA like methionine reproduces many of the effects of CR (Malloy et al., 2006) and that protein rather than total calorie intake regulates IGF-1 levels in humans (Fontana et al., 2008).' ―Della Torre​

These researchers have found that a bolus dose of free amino acids will increase IFG‐1, contrary to the epidemiological findings in Greek men. Amino acids are thought to do this by phosphorylation of the estrogen receptor (ERα). I think phosphorylation of sex receptors are a good way to translocate them into the nucleus, as phosphorylation increases the negative charge of the protein. Hence, a phosphorlyation on a protein will allow it to follow a different pH gradient and/or isoelectric point withing the cell—no 'chaperone proteins' or unicorns required (these lead to an infinite regress, as you'd then have to explain what moves the chaperone protein.)

But IFG‐1 isn't sex‐specific, and the androgen receptor appears to be just as important: Wu, Jennifer D. "Interaction of IGF signaling and the androgen receptor in prostate cancer progression." Journal of cellular biochemistry (2006):

'Despite the existing controversials on the mechanisms, all the studies have consistently showed that androgens signaling through the AR result in increased IGF-IR [the receptor] protein expression in prostate epithelium, which is associated with increased phosphorylation of IGF-IR and increased cell proliferation in response to IGF ligands.' ―Wu

'In contrast, when the tumor was in the metastatic site, IGF-IR activation enhanced AR transcriptional activity on the AAR3 promoter.' ―Wu

'Lin described that IGF-I phosphorylates AR at serines #210 and #790, whereas Gioeli failed to find any sites on the AR that were phosphorylated by IGF through a peptide terminal degeneration technique. We showed that AR phosphorylation was decreased in the presence of IGF-I and that this effect was blocked by an inhibitory IGF-IR antibody A12. Our newest study indicated that serine #16 on the AR is a potential site of dephosphorylation whereas serine #81 on the AR is a potential site of phosphorylation by IGF. The reasons for discrepancies between studies are not entirely clear.' ―Wu

'Whereas AR phosphorylation was thought to be necessary for nuclear translocation, recent data has shown that phosphorylation of AR at serine #650, which takes place after the AR is in the nucleus and bound to DNA, results in the export of AR from the nucleus. Thus, the process of dephosphorylation of specific serines on the AR may account for retention of AR in the nucleus and accentuated signaling.' ―Wu

'We also have evidence that IGF can enhance AR nuclear translocation in the absence of androgens and that this effect can be inhibited by an IGF-IR inhibitory antibody. We have also demonstrated the changes in AR compartmentalization in nuclear and cytoplasmic fractions in response to IGF using Western blot analyses. Using the AAR3 probasin reporter assay, we show a significant transactivation of the AR in the absence of androgen and enhanced AR activation in the presence of androgen by IGF-I in M12AR cells.' ―Wu

'These data indicate that even in the absence of androgen, IGF can induce transactivation of the AR. Whether this is attributed to changes in phosphorylation of the AR as we have discussed or to the recruitment of AR cofactors, or to both has yet to be determined.' ―Wu​

So the correlation between fatty acids and serum IGF‐1 could simply reflect the steroid content of the food; butter, beef, and cheese all have sex steroids which have been shown to both (1) transcribe the IGF‐1 receptor and (2) to transcribe IGF‐1 itself. In this way, the signal can be amplified as IGF‐1 transcribes for more IGF‐1 and its own receptor, a process which is increased by sex steroids. Perhaps this is how they work at such low concentrations, through secondary signalling mediated by IGF‐1.

I think dietary saturated fatty acids would correlate with sex hormones in Greek men, since they don't eat coconuts to any great extent and chocolate is rarely consumed in high amounts. More commonly eaten foods high in saturated fatty acids in Greece are dairy and beef.

The reason why protein hadn't been correlated with circulating IGF‐1 could be because (1) steroids are more powerful and (2) that leucine would be the only amino acid to consider—the one which activates the mTOR pathway the most. Carbohydrates could be negatively correlated since high‐sugar foods are relatively deficient in both leucine and sex steroids.

 

[ddjd]

some food for thought - I've always seen better hair when I'm taking nolvadex/tamoxifen which may have happened when I'd be going higher than my standard TRT dose :) This drug is an antagonist to the scalp ERbeta, agonist/antagonist to the ERalpha, causes alopecia in females... good for males? Also does it lower prolactine? I've read conflicting reports between rodents and humans

Dr. Gabe Mirkin on Health, Fitness and Nutrition. | NEW BREAKTHROUGHS IN MALE PATTERN BALDNESS

@Joeyd regarding AIs and progesterone receptors... something worth reading:

J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9.

Aromatase inhibitors: cellular and molecular effects.

Miller WR, Anderson TJ, White S, Larionov A, Murray J, Evans D, Krause A, Dixon JM.

Breast Unit, Western General Hospital, Edinburgh, Scotland, UK. [email protected]

Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in histological grading may also take place, most notably a reduction in mitotic figures. This probably reflects an influence on proliferation as most tumours (82%) show a marked decrease in the proliferation marker, Ki67. These effects are generally more dramatic than seen with tamoxifen given in the same setting. Differences between aromatase inhibitors and tamoxifen are also apparent in changes in steroid hormone expression. Thus, immuno-staining for progesterone receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming undetectable in many. This contrasts with effects of tamoxifen in which the most common change on PgR is to increase expression. Changes in proliferation occur rapidly following the onset of exposure to aromatase inhibitors. Thus, neoadjuvant studies with letrozole in which tumour was sampled before and after 14 days and 3 months treatment show that decreased expression of Ki67 occur at 14 days and, in many cases, the effect is greater at 14 days than 3 months. These early changes precede evidence of clinical response but do not predict for it. However, this study design has allowed RNA analysis of sequential biopsies taken during the neoadjuvant therapy. Based on clustering techniques, it has been possible to subdivide tumours into groups showing distinct patterns of molecular changes. These changes in tumour gene expression may allow definition of tumour cohorts with differing sensitivity to aromatase inhibitors and permit early recognition of response and resistance.

AIs seem to lower progesterone pretty bad. Bodybuilders from the 50s were using Nolvadex as an AI... which is ridiculed now. Look at their hair though. Conversely they were abusing deca-durabolin so progesterone related side effects were common.


For people who do not want to use Nolvadex, look at this thread... Vitamin E it is:

Vitamin E Is An Estrogen Receptor Antagonist

Sorry I find the scientific language hard to follow. Is it saying there's huge risk with taking Exemestane?

 

[ddjd]

@Travis do you think Aromatase inhibitors like Exemestane are very risky. I want to try them very low dose to start with like 1/16 of a pill. I have lots of problems with high Estrogen. Would be interesting to hear your opinion?

 

[ddjd]

some food for thought - I've always seen better hair when I'm taking nolvadex/tamoxifen which may have happened when I'd be going higher than my standard TRT dose :) This drug is an antagonist to the scalp ERbeta, agonist/antagonist to the ERalpha, causes alopecia in females... good for males? Also does it lower prolactine? I've read conflicting reports between rodents and humans

Dr. Gabe Mirkin on Health, Fitness and Nutrition. | NEW BREAKTHROUGHS IN MALE PATTERN BALDNESS

@Joeyd regarding AIs and progesterone receptors... something worth reading:

J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9.

Aromatase inhibitors: cellular and molecular effects.

Miller WR, Anderson TJ, White S, Larionov A, Murray J, Evans D, Krause A, Dixon JM.

Breast Unit, Western General Hospital, Edinburgh, Scotland, UK. [email protected]

Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in histological grading may also take place, most notably a reduction in mitotic figures. This probably reflects an influence on proliferation as most tumours (82%) show a marked decrease in the proliferation marker, Ki67. These effects are generally more dramatic than seen with tamoxifen given in the same setting. Differences between aromatase inhibitors and tamoxifen are also apparent in changes in steroid hormone expression. Thus, immuno-staining for progesterone receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming undetectable in many. This contrasts with effects of tamoxifen in which the most common change on PgR is to increase expression. Changes in proliferation occur rapidly following the onset of exposure to aromatase inhibitors. Thus, neoadjuvant studies with letrozole in which tumour was sampled before and after 14 days and 3 months treatment show that decreased expression of Ki67 occur at 14 days and, in many cases, the effect is greater at 14 days than 3 months. These early changes precede evidence of clinical response but do not predict for it. However, this study design has allowed RNA analysis of sequential biopsies taken during the neoadjuvant therapy. Based on clustering techniques, it has been possible to subdivide tumours into groups showing distinct patterns of molecular changes. These changes in tumour gene expression may allow definition of tumour cohorts with differing sensitivity to aromatase inhibitors and permit early recognition of response and resistance.

AIs seem to lower progesterone pretty bad. Bodybuilders from the 50s were using Nolvadex as an AI... which is ridiculed now. Look at their hair though. Conversely they were abusing deca-durabolin so progesterone related side effects were common.


For people who do not want to use Nolvadex, look at this thread... Vitamin E it is:

Vitamin E Is An Estrogen Receptor Antagonist

Have you seen this thread

Low Tesosterone, Clomid & Nolvadex

 

[ddjd]

J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9.

Aromatase inhibitors: cellular and molecular effects.

Miller WR, Anderson TJ, White S, Larionov A, Murray J, Evans D, Krause A, Dixon JM.

Breast Unit, Western General Hospital, Edinburgh, Scotland, UK. [email protected]

Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in histological grading may also take place, most notably a reduction in mitotic figures. This probably reflects an influence on proliferation as most tumours (82%) show a marked decrease in the proliferation marker, Ki67. These effects are generally more dramatic than seen with tamoxifen given in the same setting. Differences between aromatase inhibitors and tamoxifen are also apparent in changes in steroid hormone expression. Thus, immuno-staining for progesterone receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming undetectable in many. This contrasts with effects of tamoxifen in which the most common change on PgR is to increase expression. Changes in proliferation occur rapidly following the onset of exposure to aromatase inhibitors. Thus, neoadjuvant studies with letrozole in which tumour was sampled before and after 14 days and 3 months treatment show that decreased expression of Ki67 occur at 14 days and, in many cases, the effect is greater at 14 days than 3 months. These early changes precede evidence of clinical response but do not predict for it. However, this study design has allowed RNA analysis of sequential biopsies taken during the neoadjuvant therapy. Based on clustering techniques, it has been possible to subdivide tumours into groups showing distinct patterns of molecular changes. These changes in tumour gene expression may allow definition of tumour cohorts with differing sensitivity to aromatase inhibitors and permit early recognition of response and resistance.

Sorry @haidut, wouldn't normally tag you but do you think based on this study, taking low dose Exemestane would be a bad idea for combatting high Estrogen?

 

[nbznj]

Have you seen this thread

Low Tesosterone, Clomid & Nolvadex

it's basically saying what I've always been saying aka Arimidex is probably safer because not as potent. Although if you read the end of my post I'm saying that vitamin E should be a great supplement, on top of a diet that doesn't raise estrogens, of course. Have you got bloods done? Read the last post from Travis, he just explained how steroids from animals (through saturated fats) cannot be neglected. Maybe your liver health isn't too good which means you don't have a good hormonal turnover. How are your blood lipids typically? TSH?

 

[LeeLemonoil]

Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. - PubMed - NCBI

Unfortunately only the abstract still exists - but it seems in aging peripheral tissue (hairloss) glucoronides of both 3a - and 3ß-diol decrease drastically.
Given that 3ß-HSD is expressed strongly in hairloss, what does it mean - that hairloss is a condition where the scalp is unable to glucronidate DHT-metabolites like 3ß-diol - maybe this is an underdiscussed part of the pathology?

Regional scalp differences of the androgenic metabolic pattern in subjects affected by male pattern baldness. - PubMed - NCBI
Regional differences in the androgen metabolism were established in alopecic and non alopecic areas of patients affected by male pattern baldness (MPB). 5-alpha-reductase (5-alpha-R) activity was measured by the formation of dihydrotestosterone (DHT), using 3H-testosterone as substrate: this activity was higher in the alopecic areas (3.4 pmol/g tissue/h) than in the non alopecic skin (1.5 pmol/g tissue/h). 3-alpha,beta-hydroxysteroid oxoreductase (3-alpha, beta-HO) was studied using 3H-DHT as precursor and measuring the corresponding formed 3-alpha- and 3-beta-androstanediols (alpha DIOL and beta DIOL). The beta DIOL was the predominant metabolite and total 3-alpha, beta-HO activity was higher in alopecic skin (12.4 pmol/g tissue/h) than in non alopecic areas (8.4 pmol/g tissue/h). Also 17, beta-hydroxysteroid oxoreductase was measured using either testosterone or DHT as substrates: androstenedione formed from testosterone was higher in hairy skin (12 pmol/g tissue/h) than in alopecic areas (6 pmol/g tissue/h); androstanedione formed from DHT was also higher in non alopecic areas (8.1 pmol/g tissue/h) than in alopecic skin (2.8 pmol/g tissue/h). The greater formation of beta DIOL in the sebaceous glands-enriched alopecic skin supports the hypothesis for a specific role of this metabolite in the control of the sebaceous activity.


Physiopathological role of bald-scalp cytosolic proteins.
Abstract
The physiopathological role of androgen binding proteins in male pattern baldness (MPB) has been studied by using tritiated dihydrotestosterone (DHT) and methyltrienolone (R 1881) as ligands. DHT binding in bald scalp from subjects suffering from MPB is high (53 +/- 12 fmol/mg protein) in cytosol obtained from bald areas, being undetectable in hairy areas from the same subject. Since methyltrienolone does not bind in bald scalp cytosol, there must be no specific DHT receptor in this material. Several kinetic and molecular parameters of DHT binding in bald scalp cytosol and serum were similar in both samples. Only the association rate constant (k+1) was significantly higher in serum (8.8 X 10(6) M-1 min-1) than in cytosol (3.08 X 10(6) M-1 min-1). DHT binding in serum as well as the evaluation of plasma contamination in the skin samples (by nephelometric analysis) strongly suggests that DHT binding in skin cytosol is merely due to the presence of contaminating SHBG but it does not explain the lack of DHT binding in non bald areas. Thus, the possibility arises of there being a specific mechanism for the uptake of the plasmatic testosterone SHBG-complex taking place only in the hypertrophic sebaceous gland as well as the existence of active T metabolites other than DHT, probably 3 beta-androstanediol.

A possible specific receptor for 3-beta-androstanediol in the human sebaceous gland.
Dihydrotestosterone (DHT) does not seem to be the active specific metabolite of testosterone in hypertrophic sebaceous glands of subjects affected by male pattern baldness (MPB) and several results indicate that probably 3-beta-androstanediol (beta DIOL) could be an active form of testosterone in those glands. Cytosol and serum from several patients affected by MPB and subjected to hair autotransplantation, was incubated with both beta DIOL and 3-alpha-androstanediol (alpha DIOL). Binding patterns indicate that alpha DIOL binds to cytosolic proteins probably due to the contaminating sex hormone binding globulin (SHBG), whereas beta DIOL exhibits an atypical binding process in cytosol in the presence of high concentrations of non radioactive beta DIOL. This binding increases progressively up to 2 pmol/mg protein at the limit solubility conditions for the non radioactive steroid. This pattern is not observed in serum from the same patients, where the binding of beta DIOL is typically restricted to the SHBG. These results strongly suggest the existence of a specific beta DIOL-binding protein in the hypertrophic sebaceous glands and explain the lack of specific receptor for DHT in these tissues.


Also this thread is worth reading
Hair Steroid Profiling Reveals Differences In Male Pattern Baldness Between Korean & Caucas. Men

 

[ddjd]

it's basically saying what I've always been saying aka Arimidex is probably safer because not as potent. Although if you read the end of my post I'm saying that vitamin E should be a great supplement, on top of a diet that doesn't raise estrogens, of course. Have you got bloods done? Read the last post from Travis, he just explained how steroids from animals (through saturated fats) cannot be neglected. Maybe your liver health isn't too good which means you don't have a good hormonal turnover. How are your blood lipids typically? TSH?

Isnt the main point that it reduces progesterone drastically? i really dont want that!

 

[nbznj]

Isnt the main point that it reduces progesterone drastically? i really dont want that!

I'm sorry I wasn't sure if you were specifically questioning the progesterone part. Yeah it's saying that all aromatase inhibitors drastically down regulate the progesterone receptor. The idea they had was to do staining which shows the activity of a receptor. When you use AIs (and they say ALL AIs) you are going to impact the progesterone receptor. That's where I like to see what the AI is going to do in vivo and arimidex seems to be less potent.

My experience was using AIs always made my hair better than high estrogen, but still not optimal. What's optimal is a lower dose of T, no AI no SERM and high vitamin D+E, emu oil and MCT oil moisturizer, that kind of work. That seems to be my skin and hair sweet spot. I've then tried to raise T again whilst taking low doses of AIs (both exemestane or anastrozole) and it's always subpar. So my final decision was to completely stop using those ancillary drugs because they aren't a solution IMO.

What would be interesting is finding studies comparing AIs to OTC supplements.

We have a study I shared (the other topic above) that says that basically a high dose of vitamin E can be an estrogen antagonist as potent as a standard dose of nolvadex/tamoxifen, and we all know here that SERMs are to be avoided. So that is a first step.

You can do your own research for natural aromatase inhibitors and maybe try to see if there are comparisons existing between your cherished exemestane and stuff like caffeine, for example I remember another member here (and Ray Peat too) praising low dose Proviron. Mesterolone does have a mild AI effect, switches the androgen/estrogen balance towards more androgens, and is generally a very safe drug that shouldn't impact LH+FSH. I'd try that if I were you.

 

[ddjd]

I'm sorry I wasn't sure if you were specifically questioning the progesterone part. Yeah it's saying that all aromatase inhibitors drastically down regulate the progesterone receptor. The idea they had was to do staining which shows the activity of a receptor. When you use AIs (and they say ALL AIs) you are going to impact the progesterone receptor. That's where I like to see what the AI is going to do in vivo and arimidex seems to be less potent.

My experience was using AIs always made my hair better than high estrogen, but still not optimal. What's optimal is a lower dose of T, no AI no SERM and high vitamin D+E, emu oil and MCT oil moisturizer, that kind of work. That seems to be my skin and hair sweet spot. I've then tried to raise T again whilst taking low doses of AIs (both exemestane or anastrozole) and it's always subpar. So my final decision was to completely stop using those ancillary drugs because they aren't a solution IMO.

What would be interesting is finding studies comparing AIs to OTC supplements.

We have a study I shared (the other topic above) that says that basically a high dose of vitamin E can be an estrogen antagonist as potent as a standard dose of nolvadex/tamoxifen, and we all know here that SERMs are to be avoided. So that is a first step.

You can do your own research for natural aromatase inhibitors and maybe try to see if there are comparisons existing between your cherished exemestane and stuff like caffeine, for example I remember another member here (and Ray Peat too) praising low dose Proviron. Mesterolone does have a mild AI effect, switches the androgen/estrogen balance towards more androgens, and is generally a very safe drug that shouldn't impact LH+FSH. I'd try that if I were you.

Androsterone is amazing. Haidut says it's as strong as an AI

 

[ddjd]

I'm sorry I wasn't sure if you were specifically questioning the progesterone part. Yeah it's saying that all aromatase inhibitors drastically down regulate the progesterone receptor. The idea they had was to do staining which shows the activity of a receptor. When you use AIs (and they say ALL AIs) you are going to impact the progesterone receptor. That's where I like to see what the AI is going to do in vivo and arimidex seems to be less potent.

My experience was using AIs always made my hair better than high estrogen, but still not optimal. What's optimal is a lower dose of T, no AI no SERM and high vitamin D+E, emu oil and MCT oil moisturizer, that kind of work. That seems to be my skin and hair sweet spot. I've then tried to raise T again whilst taking low doses of AIs (both exemestane or anastrozole) and it's always subpar. So my final decision was to completely stop using those ancillary drugs because they aren't a solution IMO.

What would be interesting is finding studies comparing AIs to OTC supplements.

We have a study I shared (the other topic above) that says that basically a high dose of vitamin E can be an estrogen antagonist as potent as a standard dose of nolvadex/tamoxifen, and we all know here that SERMs are to be avoided. So that is a first step.

You can do your own research for natural aromatase inhibitors and maybe try to see if there are comparisons existing between your cherished exemestane and stuff like caffeine, for example I remember another member here (and Ray Peat too) praising low dose Proviron. Mesterolone does have a mild AI effect, switches the androgen/estrogen balance towards more androgens, and is generally a very safe drug that shouldn't impact LH+FSH. I'd try that if I were you.

Check out this thread, especially page 1. Really interesting about Androsterone. I think I prefer the idea of Androsterone over Exemestane

Androsterone - A Potent Steroidal Aromatase Inhibitor

 

[nbznj]

yes androsterone does make a lot of sense. I have to say I never tried it because high e2 isn't a problem of mine if I keep T around 600-700 ng/ml and keep my diet in check. Get bloods done and definitely try something more moderate before you use any AIs. I think AIs only have a place for people on TRT, and even then they should find ways of improving the T/e2 ratio through diet and other factors before resorting to AIs.