[wee2er]

Question for the specialists here, especially Lotus:

Since I keep getting stomach and bowel problems from taking too much herbs, especially RR, I have now made myself a topical tincture. I have cut up a few RR tablets and mixed the contents with a skin cream and I now apply this to my testicles and penis to get at least a little anti-androgenic effect.

What do you think? Does it make sense and can it have any effect or is it a waste of time?

Hi Nadi,
I take my RR dissolved in 5ml of warm water administered rectally. I do teh same with BO and it all works well for me.

[Nadi]

Hi,

I take milk thistle to protect my liver and I have the impression that I feel an anti-androgenic effect every time I take it. Such as a softening and temporary shrinking of the penis. Now I have asked the AI and got the following answers:

"The anti-androgenic effect of milk thistle can be explained by several mechanisms:

Inhibition of androgen synthesis
Studies suggest that components of milk thistle can reduce the production of androgens:

• Silymarin, the main active ingredient in milk thistle, inhibits enzymes such as 5α-reductase and 17β-hydroxysteroid dehydrogenase. These enzymes are involved in the synthesis of testosterone and dihydrotestosterone (DHT)1.
  
• By inhibiting these enzymes, less testosterone is converted into the more potent DHT, which leads to a reduction in androgen activity
  

Blockade of androgen receptors
Components of milk thistle can also interact directly with androgen receptors:

• Studies show that silymarin can block the binding of androgens to their receptors.
  
• This prevents androgens from exerting their effect in the target tissues."
  

Has this been discussed here before and have you had similar experiences?

[Lotus]

Hi Nadi, milk thistle has been discussed at Nexum. I have additional information covering MT if anyone is interested.

Milk Thistle inhibits testosterone:

Time- and Concentration-Dependent Inactivation of Testosterone Metabolism of P450 3A4 by Silybin. 6 -Hydroxytestosterone was the major metabolite detected when testosterone was incubated with purified recombinant P450 3A4 in a reconstituted system in the presence of NADPH. Silybin inhibited the metabolism of testosterone by P450 3A4 in a time-, concentration-, and NADPH-dependent manner.   

SILYBIN INACTIVATES CYTOCHROMES P450 3A4 AND 2C9 AND INHIBITS MAJOR HEPATIC GLUCURONOSYLTRANSFERASES 
http://dmd.aspetjournals.org/content/dmd...7.full.pdf

From the study, approximately 250mg of SILYBIN (milk thistle) was used to inhibit Testosterone, and metabolized in about 9 to 18 min. Here's the real find though:

silybin (milk thistle) inhibits both phase I and phase II enzymes which inactivates P450s 3A4. Additionally, Silybin was approximately 14- and 20-fold more selective at inhibiting UGT1A1 (aka-Glucuronidation) which is an important metabolic pathway in the liver such as steroid hormones.

Now, from my calculations using pseudofirst-order kinetics, milk thistle decreases T approximately 62% in 9-18min.


Time- and Concentration-Dependent Inactivation of the 7EFC Activity of P450 2C9. As shown in Fig. 4, with P450 2C9 the silybin-mediated inactivation of the 7EFC O-deethylation activity was also time-, concentration-, and NADPH-dependent. Approximately 35% activity loss was seen in 15 min when 50 M silybin was used. The inactivation exhibited pseudofirst-order kinetics. The double- reciprocal plot of the values of the initial rate constants versus the silybin concentrations gave a KI of 5 M, a kinact of 0.14 min 1, and t1/2 of 7 min. 

Alternatively, the following method below is used to lower DHT, though it's complexity for day to day use seems unlikely.

Transcriptional regulation of human UDP-glucuronosyltransferase genes.
Hu DG1, Meech R, McKinnon RA, Mackenzie PI.
Author information

Abstract
Glucuronidation is an important metabolic pathway for many small endogenous and exogenous lipophilic compounds, including bilirubin, steroid hormones, bile acids, carcinogens and therapeutic drugs. Glucuronidation is primarily catalyzed by the UDP-glucuronosyltransferase (UGT) 1A and two subfamilies, including nine functional UGT1A enzymes (1A1, 1A3-1A10) and 10 functional UGT2 enzymes (2A1, 2A2, 2A3, 2B4, 2B7, 2B10, 2B11, 2B15, 2B17 and 2B28). Most UGTs are expressed in the liver and this expression relates to the major role of hepatic glucuronidation in systemic clearance of toxic lipophilic compounds. Hepatic glucuronidation activity protects the body from chemical insults and governs the therapeutic efficacy of drugs that are inactivated by UGTs. UGT mRNAs have also been detected in over 20 extrahepatic tissues with a unique complement of UGT mRNAs seen in almost every tissue. This extrahepatic glucuronidation activity helps to maintain homeostasis and hence regulates biological activity of endogenous molecules that are primarily inactivated by UGTs. Deciphering the molecular mechanisms underlying tissue-specific UGT expression has been the subject of a large number of studies over the last two decades. These studies have shown that the constitutive and inducible expression of UGTs is primarily regulated by tissue-specific and ligand-activated transcription factors (TFs) via their binding to cis-regulatory elements (CREs) in UGT promoters and enhancers. This review first briefly summarizes published UGT gene transcriptional studies and the experimental models and tools utilized in these studies, and then describes in detail the TFs and their respective CREs that have been identified in the promoters and/or enhancers of individual UGT genes.

In this study DHT and EGF decreased the protein level of UGT2B17  by 75% ,  that was correlated with a decreased production of DHT-G by 73%. I take that to mean decreasing a protein like UGT2B17 it decreases (inhibits DHT) by 73%.

Differential Regulation of Two Uridine Diphospho-Glucuronosyltransferases, UGT2B15 and UGT2B17, in Human Prostate LNCaP Cells*
http://press.endocrine.org/doi/pdf/10.12...138.7.5226

[Nadi]

Hi Lotus,

so nice to read from you again! I hope you are doing well? Thank you very much for your explanations. If I have understood correctly (I am a blonde ), these scientific findings coincide with my anecdotal experiences.

The calming phase, which I attribute to the anti-androgenic effect, always sets in about 10 to 20 minutes after taking it.

I will therefore continue to take MT all the more to detox my liver.

[sissycdnikki]

hi i enjoy pumpkin seeds what is the good or bad effects on my journey i have been on hrt for 2 years

[Stevenator_]

At the bottom of each thread is a keyword search function for that particular thread. Typing "pumpkin seeds" in that keyword search returns a lot of hits showing that pumpkin seeds do block 5ar. It also appears that they are high in zinc.

This keyword search function will yield years of research that Lotus has put into her science threads, and in turn is a great service for those seeking information related to our cause.

Best of Luck to You.