estrogen blockers "good or bad"?

[wilson6]

Orthoprefest is a combination of estradiol and progestin.

Estratest is a combination of conjugated estrogens (mostly sodium estrone sulfate) and methyltestosterone.

Methyl-T is useless for building muscle and causes mood problems in some. The amount in Estratest is 2.5 mg. Most is extensively metabolized by the liver leaving very little to act peripherally. Moreover, unlike T-gel, Methyl-T will lower HDL cholesterol even in low doses.

I would think (MS comment here) that if I were post-menopausal, I would be taking a small amount of estradiol in a natural form and also a small amount of progestin also natural form to oppose it, and testosterone gel not Methyl-T.

W6

 

[THeMaCHinE]

I have to look this up but, OX for example at least in female rats upregulates a CYP enzyme only upregulated in male rats due to T, might be 3A4 but I can't remember, anyhow it might affect synthetic estrogen/progesterone metabolism and could possibly alter clinicial effectiveness. Same applies to other agents such as Milk Thistle.

W6

So, when she's on cycle (if she cycles again), it's a good idea to use an alternate form of bc? (condoms, etc.)

 

[wilson6]

I'd certainly recommend it. As Remo said in Casino, "why take a chance".

W6

 

[wilson6]

This is what I was looking for.

Author
Waskiewicz, M J; Choudhuri, S; Vanderbeck, S M; Zhang, X J; Thomas, P E

Title
Induction of "male-specific" cytochrome P450 isozymes in female rats by oxandrolone.

Drug metabolism and disposition: the biological fate of chemicals. vol. 23, no. 11 (1995 Nov): 1291-6.

Abstract
Oxandrolone (OXA) (5 alpha-androstan-2-oxa-17 alpha-methyl-17 beta-ol-3-one) is a clinically useful, synthetic, anabolic androgen steroid hormone. OXA was administered to rats orally twice daily for 3 days at 75 mg/kg to study the effect on hepatic cytochrome P450 (P450) isozymes. Western blots were performed on the hepatic microsomal fraction and probed with isozyme-specific monoclonal antibodies. Microsomes were also tested for catalytic activity in a testosterone metabolism assay. Data from Western blots revealed that, in female rats, there were increased levels of two male-specific isozymes, P4502C11 and P4503A2, as well as P4503A1. In contrast, male rats showed little or no change in expression of these P450 isozymes after OXA treatment. The 6 beta-hydroxylation of testosterone, which is catalyzed predominantly by P4503A1 and P4503A2, increased approximately 10-fold in female rats after treatment with OXA (from 0.05 +/- 0.01 to 0.52 +/- 0.05 nmol/min/mg protein), but only relatively small changes were seen in the male rats (from 1.02 +/- 0.05 to 1.38 +/- 0.07 nmol/min/mg protein). To investigate if the changes seen in P4503A1 and P4503A2 protein and activity were caused, at least in part, by an increase in mRNA levels, Northern blot analysis was performed. P4503A2 mRNA was increased dramatically in the female rat liver after OXA treatment, but only small increases in P4503A1 mRNA were seen. This data indicate that OXA induces P450 isozymes in the female but not in the male rat liver, probably through transcriptional activation, and some of these induced isozymes are male-specific.

 

[THeMaCHinE]

Interesting stuff ... the information about testosterone hydroxylation is interesting too.

It's also interesting to note that grapefruit juice (which was discussed by MS as a no-no above) effects the P450 isozyme. (Although it's the CYP3A4 isomer vs. those discussed here.)

Thanks for digging that up. Looks like we can plan on wrapping that rascal if she decides to cycle again ... lol ...

 

[MS]

I would go with Tri-est plus topical progesterone and testosterone for post menopause.

The rat enzymes upregulated by ox do not show the same gender differences in humans. In other words, 2C11 and 3A2 cannot be considered 'male-specific' in humans, and I doubt their upregualtion would have a huge impact on oral contraceptive clearance anyway. But when it comes to cantraception, my motto is also "better safe than sorry" and I would double up 24/7/365 if it were me!

 

[THeMaCHinE]

I would double up 24/7/365 if it were me!

 

[wilson6]

CYP3A4 metabolizes a number of drugs including OCs. It is upregulated by St John's Wort as well.

W6

 

[MS]

Cyp 3A4 is inhibited by grapefruit juice but increased by St John's Wort. In the grapefruit case you would predict excessively high plasma levels of OCs if taken with juice (can you say excess hormones!!!), in the St John's wort sitch you would expect decreased levels of hormone which could reduce the OCs effectiveness (can you say baby on the way). But in reality, the dose of St John's wort taken by most folks for depression doesn't significantly inhibit Cyp 3A4 enough to cause problems, but it can interfere with other drugs, mainly through 3A4 to a small extent, and increased P-glycoprotein expression to a larger extent.

 

[THeMaCHinE]

Cyp 3A4 is inhibited by grapefruit juice but increased by St John's Wort. In the grapefruit case you would predict excessively high plasma levels of OCs if taken with juice (can you say excess hormones!!!), in the St John's wort sitch you would expect decreased levels of hormone which could reduce the OCs effectiveness (can you say baby on the way). But in reality, the dose of St John's wort taken by most folks for depression doesn't significantly inhibit Cyp 3A4 enough to cause problems, but it can interfere with other drugs, mainly through 3A4 to a small extent, and increased P-glycoprotein expression to a larger extent.

I remember that grapefruit juice also effected p-glycoproteins (can't remember which way though) in the intestinal track -- this is what caused the delay or blocking of absorption in some drugs/supps.

Interesting about St. John's -- I didn't know that. I can't remember what the active component of St. John's is, but I wonder if it's intrinsic to that compound as well (or only the plant as a whole)?