ඉදිරියේ රාළ;20824084 said:
Prove me Wrong by showing that Heat and Acidity has no relation to Hormone Imbalance, Otherwise You are Psycho
I'm talking about scientifically proven theories which are accepted by western medicine which clearly states that gastric acid has no influence on hormonal systems.
Can you prove what you say is correct?
I will attach comprehensive description of causes for gynaecomastia from upto date.
PATHOPHYSIOLOGY — The basic mechanisms of gynecomastia include a decrease in androgen production, an increase in estrogen production, or increased availability of estrogen precursors for peripheral conversion to estrogen. Androgen receptor blockade and increased binding of androgen to sex hormone-binding globulin (SHBG) are other mechanisms.
There does not appear to be any difference in the responsiveness of the male or female breast glandular tissue to hormonal stimulation. The amount of glandular proliferation and ductal differentiation depends upon an individual's breast tissue sensitivity, the hormonal milieu, and the duration and intensity of hormonal stimulation.
Estrogens induce ductal epithelial hyperplasia, ductal elongation and branching, proliferation of the periductal fibroblasts, and an increase in vascularity. The histologic picture is similar in male and female breast tissue after exposure to estrogen. In comparison, luteal phase progesterone in women leads to acinar development that is not seen in males [21].
The various conditions associated with gynecomastia are usually thought to represent an imbalance between the stimulatory effect of estrogen and the inhibitory effect of androgen (figure 3) [22,23]. The factors that define the net estrogen/androgen balance are (table 4):
●The production of these steroids or their precursors by the three steroid-producing tissues (the placenta, the adrenals, and the testes)
●The extraglandular conversion of androgens to estrogens, such as in adipose tissue
●The circulating concentration of SHBG
●The hormone target cells' ability to respond to androgens and estrogens
In utero — During pregnancy, the placenta transforms dehydroepiandrosterone and dehydroepiandrosterone sulfate (derived from both the mother and fetus) to estrone (E1) and estradiol (E2), which enter the fetal circulation and stimulate breast glandular proliferation, resulting in transient neonatal gynecomastia. (See "Placental development and physiology", section on 'Steroid hormones'.)
Estrogen in men — In adult men, 95 percent of the circulating testosterone, 15 percent of the E2, and less than 5 percent of E1 is directly secreted by the testes (figure 3). The major androgen secreted by the adrenal glands is androstenedione. Most of the circulating E2 and E1 are derived from the extraglandular conversion of testosterone and androstenedione to E2 and E1, respectively, by tissues including liver, skin, fat, muscle, bone, and kidney, all of which contain an aromatase enzyme. There is also a substantial amount of interconversion between testosterone and androstenedione and between E2 and E1 in extraglandular tissues via 17-hydroxysteroid dehydrogenase (17-ketosteroid reductase) enzyme [21,24,25]. (See "Male reproductive physiology", section on 'Androgen synthesis'.)
Sex hormone-binding globulin — The majority of androgens and estrogens that enter the circulation are relatively tightly bound to SHBG and are weakly bound to albumin. SHBG has a higher affinity for androgens than for estrogens and, therefore, any substance that displaces sex hormones from SHBG will tend to displace quantitatively more estrogens than androgens. The unbound or weakly bound androgens and estrogens enter the target cells and lead to hormone action [26,27]. (See "Male reproductive physiology", section on 'Transport of gonadal steroids'.)
Imbalance between estrogen and androgen — An imbalance between estrogen and androgen action will occur if there is an absolute increase in free estrogens, a decrease in endogenous production of free androgens, an increase in the free estrogen-to-free androgen ratio, androgen insensitivity, or an estrogen-like effect of drugs (figure 3). Some patients with gynecomastia, for example, have enhanced sensitivity of the breast tissue to normal circulating estrogen levels even in the presence of normal circulating androgen concentrations. This may reflect increased aromatization of androgens to estrogens in the breast tissue itself, as increased aromatase activity has been found in pubic skin fibroblasts of patients with gynecomastia [28].
Obesity — In some studies, body mass index (BMI) is positively correlated with both breast diameter and the presence of gynecomastia in both adolescents and adults [16,29]. Breast adipose tissue contains the aromatase enzyme complex that converts testosterone and androstenedione to E2 and E1, respectively. Thus, it is hypothesized that an increase in breast adipose tissue due to generalized weight gain may increase local estrogen production, which in turn may stimulate breast glandular tissue proliferation in a paracrine fashion. In addition, the increase in breast fat with weight gain may lead to pseudogynecomastia, which may or may not be associated with true gynecomastia. (See "Causes of secondary hypogonadism in males", section on 'Obesity'.)
CAUSES OF GYNECOMASTIA
Physiologic — As noted above, physiologic gynecomastia is common and has a trimodal distribution occurring in neonatal, pubertal, and older males. The estimated prevalence of asymptomatic gynecomastia in these three age groups is 60 to 90 percent in neonates, 30 to 60 percent in adolescents, and 35 to 65 percent in men ages 50 to 69 years [2].
Puberty — Most studies in pubertal boys with gynecomastia have found no differences in single-point measurements of serum concentrations of testosterone, estradiol, estrone, or gonadotropins from those in normal boys [7,9,30,31]. However, some reports have shown a transient increase in estradiol concentration at the onset of puberty in boys who develop gynecomastia [7]. These boys may also have wider fluctuations of estradiol levels, with an absolute increase in 24-hour concentration of estradiol, which may reflect increased conversion of adrenal androgens to estrogens [10,32]. Adrenal androgen secretion rises during adrenarche, which occurs independently of and before the maturation of the hypothalamic-pituitary-gonadal axis (gonadarche).
During puberty, the serum estradiol concentrations rise to adult levels before the testosterone concentration. It is likely that this transient imbalance accounts for much of the estrogen/androgen imbalance that leads to pubertal gynecomastia [10,14,31,33].
Leptin and insulin-like growth factor 1 (IGF-1) have been found to be elevated in boys with pubertal gynecomastia in comparison to those without [34-37]. The finding that pubertal gynecomastia occurs in a temporal association with peak height velocity, the time when IGF-1 levels also peak, suggests that together with estrogens, IGF-1 may play a role in the genesis of pubertal gynecomastia.
Pubertal gynecomastia usually resolves spontaneously within six months to two years of onset, but in some instances, may persist after completion of puberty into adulthood, resulting in persistent pubertal gynecomastia.
Drugs — There are many drugs that have been associated with gynecomastia (table 3). Drugs with the best evidence for an association with gynecomastia include spironolactone, cimetidine, ketoconazole, recombinant human growth hormone, estrogens, human chorionic gonadotropin (hCG), antiandrogens, gonadotropin-releasing hormone (GnRH) agonists, and 5-alpha-reductase inhibitors [38]. The pathophysiologic mechanism for some, such as estrogens or antiandrogens, is quite clear. However, for others such as spironolactone, the mechanisms are likely more complex.
Spironolactone can increase the aromatization of testosterone to estradiol (E2), decrease the testosterone production rate by the testes, and displace testosterone from sex hormone-binding globulin (SHBG), thereby increasing its metabolic clearance rate. Spironolactone also acts as an antiandrogen by binding to androgen receptors and displacing or preventing binding of testosterone and dihydrotestosterone to their receptors [26,39].
In a placebo-controlled trial of low-dose spironolactone (25 to 50 mg/day) for heart failure, endocrine side effects (gynecomastia, breast pain, impotence, and decreased libido) were seen in 10 percent compared with 3 percent in the placebo group [40]. Gynecomastia will occur in almost every male who takes a large dose of spironolactone (≥100 mg/day), eg, to treat men with liver failure or hypertension due to aldosterone excess [41].
In contrast, in a study of eplerenone (a newer selective mineralocorticoid receptor antagonist) in over 6500 patients with heart failure, gynecomastia, impotence, or breast pain occurred with equal frequency in the eplerenone and placebo groups (1.0 versus 1.1 percent) [42]. (See "Use of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction".)
For many of the drugs listed in the table, a clear-cut relationship between the drug ingestion and gynecomastia has not been established (table 3). For most drugs, the presumed relationship has been based upon epidemiologic studies or challenge-rechallenge studies in small numbers of individual patients [38,39].
Drugs within the same class do not all cause gynecomastia to the same extent. Among the calcium channel blockers, nifedipine has the highest frequency of gynecomastia and diltiazem the lowest [39,43]. Thus, in an older man who is at increased risk of gynecomastia simply on the basis of age, diltiazem would be preferable to nifedipine.
Another example is the use of H2-receptor or proton-pump blockers; the incidence of gynecomastia is highest with cimetidine followed by ranitidine and lowest with omeprazole [44]. Thus, omeprazole would be a better choice in an older individual with other risk factors for developing gynecomastia.
ART — The breast enlargement that is seen in men with human immunodeficiency virus (HIV) receiving antiretroviral therapy (ART) is usually due to fat tissue (lipomastia or pseudogynecomastia) as part of a fat redistribution syndrome (lipodystrophy) [45]. However, cases of true gynecomastia have also been described, thought to be due to coexisting hypogonadism or possible estrogen-like effects of some drugs, in particular, efavirenz [46]. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy" and "Treatment of HIV-associated lipodystrophy".)
Hormone therapy for prostate cancer — Gynecomastia is common in men with prostate cancer undergoing androgen deprivation therapy, in particular with bicalutamide. The prevalence is as high as 75 percent when antiandrogen monotherapy is used, but is reduced to approximately 15 percent in men treated with total androgen blockade (combined GnRH agonist with an antiandrogen). When antiandrogens are used as monotherapy, much higher doses are used, eg, bicalutamide 150 mg/day versus 50 mg/day if combined with a GnRH agonist. (See "Side effects of androgen deprivation therapy", section on 'Gynecomastia' and "Overview of the treatment of disseminated prostate cancer", section on 'Androgen deprivation therapy'.)
Herbal products — Tea tree oil and lavender oil, plant-derived oils that are available as over-the-counter skin care products (lotions, soaps, and shampoos), have been associated with gynecomastia. This was illustrated in a report of three prepubertal boys in whom gynecomastia developed after repeated use of skin products containing the oils [47]. Both oils had weak estrogenic and antiandrogenic properties in in vitro studies, and the gynecomastia resolved when the skin products were discontinued. Other environmental substances with estrogenic or antiandrogenic properties have also been reported to cause gynecomastia [48-50]. Soy protein formulas, which contain high concentrations of phytoestrogens, were not associated with gynecomastia in one study in children [51].
Idiopathic — Gynecomastia in adults is often multifactorial. Aging per se is associated with an increase in body fat relative to the lean body mass. Adipose tissue is an active site of extraglandular aromatization of testosterone to E2 and of androstenedione to estrone (E1). In addition, there tends to be a gradual decrease in testosterone production by the aging testes and an increase in SHBG levels, resulting in a fall in the free testosterone concentration with a reciprocal increase in the luteinizing hormone (LH) level [24,52]. These two factors probably account for most patients who have “idiopathic” gynecomastia. Older men are also more likely to take medications associated with gynecomastia than are younger men.
Cirrhosis — The prevalence of gynecomastia in cirrhotic patients is as high as 67 percent; however, this may not be significantly different from control patients drawn from the same population [23,53]. Cirrhosis is accompanied by several changes that probably explain the development of gynecomastia: an increased production rate of androstenedione from the adrenals, enhanced aromatization of androstenedione to E1, and increased conversion of E1 to E2 [54]. Additionally, many patients receive high doses of spironolactone, which can contribute to the pathogenesis of gynecomastia in this population. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Chest findings'.)
Starvation and refeeding — Several studies were carried out on American prisoners of war who were freed at the end of World War II. About 10 percent had developed gynecomastia during starvation, while between 5 and 50 percent noted breast tenderness, pain, and enlargement within two to three months of refeeding after release [55]. Prior to refeeding, approximately 80 percent reported erectile dysfunction, 85 percent had decreased libido, and 73 percent showed testicular atrophy [56]. (See "Causes of secondary hypogonadism in males".)
During starvation, both gonadotropin and testosterone levels were probably reduced, while estrogen production was probably normal due to normal estrogen production from adrenal precursors. These changes will promote the development of gynecomastia. During refeeding, gonadotropins rise, resulting in both an increase in testosterone secretion and a marked elevation in E2 production that mimics normal puberty [56]. Thus, patients who develop refeeding gynecomastia may be said to have undergone a "second puberty." (See "Normal puberty", section on 'Boys'.)
Male hypogonadism — Primary hypogonadism can be due to a congenital abnormality such as Klinefelter's syndrome or an enzymatic defect in the testosterone biosynthetic pathway, or to testicular trauma, infection, infiltrative disorders, vascular insufficiency, or aging (see "Causes of primary hypogonadism in males"). The associated reduction in testosterone production leads to a decrease in the serum testosterone concentration and a compensatory rise in LH release. The excess LH results in enhanced Leydig cell stimulation with inhibition of the 17,20-lyase and 17-hydroxylase activities and increased aromatization of testosterone to E2; the net effect is an increase in E2 relative to testosterone secretion [57].
Secondary hypogonadism due to a hypothalamic or pituitary abnormality may also be associated with gynecomastia. In these patients, the production of LH is deficient, resulting in a low testosterone production rate and low E2 production from the testes. However, the adrenal cortex continues to produce estrogen precursors that are aromatized in extraglandular tissue; the result is an estrogen/androgen imbalance.
Men with hyperprolactinemia may develop gynecomastia due to prolactin's effect on reducing the secretion of gonadotropins leading to secondary hypogonadism. Prolactin itself will stimulate milk production in breast tissue that has been primed by estrogen and progesterone, but does not directly cause gynecomastia itself.
Testicular neoplasms — Germ cell tumors account for approximately 95 percent of testicular neoplasms; between 2.5 percent and 6 percent of affected patients have gynecomastia at the time of presentation [57]. The gynecomastia is associated with secretion of hCG by foci of choriocarcinoma or trophoblastic cells in the tumor (table 3). (See "Anatomy and pathology of testicular tumors".)
Hyperthyroidism — Gynecomastia has been reported in as many as 25 to 40 percent of men with hyperthyroidism due to Graves' disease, although one study suggests that the actual prevalence is less than 10 percent [64-67]. Serum LH levels are often elevated, contributing to increased E2 relative to testosterone production by Leydig cells [68,69]. There is also enhanced aromatization of testosterone to E2 and of androstenedione to E1 in extraglandular tissues [70]. This results in increased concentration of SHBG. Free testosterone levels are normal or low, while free E2 levels are elevated. Thus, gynecomastia results from the combination of decreased free androgen levels combined with the overproduction of estrogens. (See "Overview of the clinical manifestations of hyperthyroidism in adults", section on 'Genitourinary'.)
Chronic kidney disease — Gynecomastia occurs in about 50 percent of patients treated with maintenance hemodialysis [71]. The primary cause of the gynecomastia appears to be Leydig cell dysfunction. Serum testosterone levels are low and gonadotropins are appropriately elevated; the metabolic clearance of LH is also reduced [72]. Gynecomastia may occur following renal transplantation as gonadal function improves ("refeeding gynecomastia") and/or the use of transplantation medications such as cyclosporine. (See "Sexual dysfunction in uremic men", section on 'Gynecomastia'.)
by the way , patients are now beginning to know who the true pathetic liars are.
