Androgens and GERD, acid reflux, and peptic ulcer [by Type-IIx]

[Type-IIx]

Author: Type-IIx


Gastric mucosal susceptibility and ulcerogenic effects
acid reflux; peptic ulcer


GERD: Gastroesophageal reflux disease (GERD) occurs when stomach acid flows back into the tube connecting your mouth and stomach (esophagus). This backwash (acid reflux) can irritate the lining of the esophagus.

Androgens are ulcerogenic and enhance the susceptibility of gastric mucosa to the peptic action of gastric juice [1]. Estrogens are protective: females appear to be protected against both gastric hypersecretion and peptic ulcers in those periods in their lives when circulating estrogens are high [1].

Pronounced sex difference in acid reflux and peptic ulcer
The sex difference in the male rat excreting lesser free histamine than the female is ascribed to the sex-related efficiency in the male for metabolic inactivation of histamine via methylation as the principal catabolic pathway [2]... Testosterone increases the proportion of methylhistamine in urine [2]. The female kidney, most pronounced in pregnancy, forms more histamine, and in pregnancy, the activity of histidine decarboxylase (histamine formation capacity of tissues, especially kidney and fetal tissue) is markedly increased [2].

Estrogen provokes a dose- and time- dependent increase in histamine excretion. Progesterone does not alter histamine excretion. Testosterone provokes a striking dose- and time- dependent decrease in histamine excretion. Testosterone virtually abolishes kidney histidine decarboxylase activity.


Histamine and the gut
Histamine serves a function in gastric acid secretion via the H₂ receptors (H₂R). H₂R antagonists potently inhibit acid (HCl) secretion [3].

Gastric mucosa is markedly rich in histamine, and there is a selective accumulation of histamine related to acid secretory cells. Gastric acid secretion is strongly stimulated by histamine and a number of methyl histamine analogs, including n(Me)histamine, n'n'dimethyl histamine, and 4-(Me)histamine [3].

- Cimetidine antagonizes histamine by competitive inhibition of H₂ receptors (H₂R) located in gastric parietal cells ⇒ ↓gastric acid secretion & volume & acidity

Histamine interacts with other stimuli of gastric acid secretion: there is potentiation in the parietal cell between histamine, acetylcholine, and gastrin [3]. Other stimuli of gut acid secretion include: food, caffeine, distension, vagal, and other cholinergic agents [3].

Relevant organs
Gastric (stomach) muscle contracts with H₁R stimulation & relaxes with H₂R stimulation
- Gastric emptying is unaffected by H₂R antagonists

Pylorus:
- Histamine has unclear effects on, but does affect, phasic contractions of the pyloric sphincter (frequency, amplitude, duration) via neural & myogenic H₁R

Intestine:
- Ileal contraction with histamine is a classic H₁ effect

Gallbladder:
- H₁R mediate gallbladder contraction by histamine; H₂R mediate gallbladder relaxation
...Blockade of H₂R augments the response to [hormonal agents], suggesting that histamine may modify the response to this class of agents...
[3]


Cimetidine ✖
Tagamet

- Cimetidine antagonizes AR by cytosolic binding & inhibits gastric acid secretion
- antagonizes H2 histamine receptor-mediated gastric acid secretory response
- stimulates plasma prolactin

Also:
- binds cytochrome P-450 as a type II ligand, inhibiting its function, causing reduced metabolism of exogenous pharmacological agents (via cyt. P-450)
- alters hepatic metabolism of estrogens (↓2- & 16α- hydroxylation of E₂)
- alters hepatic metabolism of androgens (↓formation of polar metabolites [hydroxylated derivatives], producing a marked increase in 3-androstenediol, the fully reduced androgen)
- ↓6β-, 7α-, and 16α- hydroxylation of T (20, 21) [4]


Ranitidine, Famotidine, Nizatidine ✓
Zantac, Pepcid, Axid

Ranitidine and famotidine (2d gen. H₂R antagonists) do not affect cytochrome P-450 metabolism, androgen nor estrogen metabolism [4].

Nizatidine did not antagonize AR, had a less potent and consistent effect on plasma prolactin increase.

______________________________
References:

[1] Kowalewski, K., Schier, J. F., & Chmura, G. (1970). Effect of Sex Hormones on Gastric Secretion and on Gastric Mucosa in Oophorectomized Histamine Stimulated Rats. Digestion, 3(1), 13–19. doi:10.1159/000196983
[2] HENNINGSSON, S. S. G., & ROSENGREN, E. (1972). Alterations of histamine metabolism after injections of sex hormones in mice. British Journal of Pharmacology, 44(3), 517–526. doi:10.1111/j.1476-5381.1972.tb07288.x
[3] Hirschowitz, B. I. (1985). Histamine and the Gut. Allergy and Asthma Proceedings, 6(1), 21–27. doi:10.2500/108
854185779048942
[4] Galbraith, R. A., & Jellinck, P. H. (1989). Differential effects of cimetidine, ranitidine and famotidine on the hepatic metabolism of estrogen and testosterone in male rats. Biochemical Pharmacology, 38(12), 2046–2049. doi:10.1016/0006-2952(89)90507-8

 

[Pizza15]

So

Ranitidine, Famotidine, Nizatidine

are the go-to drugs to fix GERD issues on androgens?

 

[Type-IIx]

So

Ranitidine, Famotidine, Nizatidine

are the go-to drugs to fix GERD issues on androgens?

Proton pump inhibitors (PPIs): e.g., esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec) are also effective. They work by a different mechanism (irreversibly binding to H⁺/K⁺ ATPase ["proton pump"] in parietal cells). Using these chronically for as few as 8 weeks (>= 8 weeks), upon cessation, rebound hyperacidity (hypergastrinemia) is likely, therefore PPIs should be slowly tapered [1, 2]. Other long-term use considerations include risk of fractures, hypomagnesemia, C. diff.-associated diarrhea, vitamin B12 deficiency... [3].

References:
[1] Sheen E, Triadafilopoulos G. Adverse effects of long-term proton pump inhibitor therapy. Dig Dis Sci N. Y. 2011;56(4):931-950.
[2] Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Ther Adv Gastroenterol. 2012;5(4):219-232.
[3] Wilhelm SM, Rjater RG, Kale-Pradhan PB. Perils and pitfalls of long-term effects of proton pump inhibitors. Expert Rev Clin Pharmacol. 2013;6(4):443-451.

 

[Muay Thai]

I have gerd and abused androgens in my 20s

 

[Muay Thai]

r

So

Ranitidine, Famotidine, Nizatidine

are the go-to drugs to fix GERD issues on androgens?

ranitidine was pulled off the market a few years back...pantoprazole is what I have been on for years. PPI inhibitor i believe, nephrologist had me stop taking it.

 

[gains4000]

My GI DR told me androgens like nandrolone and oxymetholone cause a lot of his patients to be bodybuilders. he perscribes pantoprazole. I don't use it anymore. i prefer natural suppplements,

 

[Proformance121]

This article was very timely for me...I just started an oral pro hormone cycle...today, and felt the positive effects almost immediately and had a great workout. However, after my post-workout meal I encountered severe GERD symptoms: bloating, belching, acid reflux, etc. Prior to today I was eating just fine with no GERD issues. I thought maybe the cause was the liposomal delivery system of the new non-methylated PH's, but I didn't think about the fact that androgens like anadrol are notorious for causing gastro-issues. I remembered I had a stash of famotidine and after about 30 minutes of taking the tablet I felt better.

I had stocked up on famotidine during COVID as there were some studies floating around that seemed to suggest that the histamine action of the drug actually inhibited an enzyme that was key for the viruses replication. https://www.science.org/content/art...ly-tests-heartburn-remedy-against-coronavirus