Nandrolone at Defy Medical

[madman]

My results says direct, so probably an RIA. Just assuming it doesn’t cross-react with free nandrolone as if it did it should have been way higher than the reference @ 7.2-24.0 pg/ml. I’ll recheck using mass spec the next time I do bloodwork

Yes but it is still not an accurate method for testing FT.

You would need to have it tested using Equilibrium Dialysis or Ultrafiltration to know where it truly sits especially in cases of altered SHBG.

 

[madman]

Well said. Don’t worry about anyone telling u reasons to switch things up. Just ignore them and continue enjoying ur life. Most people don’t understand nandrolone all that well, so I can see why it can be confusing/ hard for them to understand why it works as a base

Main things to remember are, that nandrolone doesn’t convert much into E2, but does convert into E1, at a higher rate than test does. E1 might be weaker than E2, but can still carry out the same functions that E2 does. So how much E2 a person has in their system, while using a nandrolone base, doesn’t tell the whole story, in regards to estrogen receptor activation

The other thing to consider, is that yes, nandrolone doesn’t convert into DHT, it converts into DHN, and DHN is a lot weaker than DHT, but DHN still activates the same receptors, in the same ways, as DHT, just less than DHT would. But this is actually a good thing. It allows the person to have the same activation on receptors that DHT would have, but again at a weaker level, so u can get the benefits of DHT, without some of the sides that come with high DHT, while still being able to have decently high androgen levels.

So the benefits of using a nandrolone base are mainly that u can have higher androgen levels, while not having equally as high E2, dht and prolactin levels, like someone might have while on a test base, while keeping androgen levels on the higher end

Typical sheep!

Need to stop watching/posting those kiddie videos!

Come again?

Estradiol is critical!

Again for the last f**king time!

More importantly, Ts metabolites estradiol and DHT are needed in healthy amounts to experience the full spectrum of testosterones beneficial effects on (cardiovascular health, brain health, libido, erectile function, bone health, tendon health, immune system, lipids, and body composition).

Again tread lightly on how low your drive your e2!

Critical point here!

*serum estradiol (E2) needs to be above 20 pg/mL to prevent bone loss

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*Afterwards, the androstenedione can be either converted to testosterone by 17β-hydroxysteroid dehydrogenase (17β-HSD), or to E1 by the aromatase enzyme (CYP19A1)[33]. Then, 17β-HSD catalyzes the conversion of E1 to E2 [33]




2. Estrogens

2.1. Types of estrogens and primary sites of production

Estrogens are steroidal sex hormones that include estrone (E1),estradiol (E2), estriol (E3), and estetrol (E4) [25]. The predominant circulating female hormone is E2, which is commonly referred to as"estrogen", due to its physiological importance and prevalence during the reproductive years [16,25]. E1 is commonly detected at higher levels after menopause, while E3, and E4 are produced only during pregnancy[26].

The ovaries, specifically the granulosa cells, are the primary source of E2 in premenopausal women, acting as a circulating hormone on distal tissues [25,27]. In men, E2 is produced in minute amounts by the testes [28]. Estrogens are also produced in extra-gonadal sites such as adipose tissue, brain, skin, muscles, bones, vascular endothelium,vascular smooth muscles, intestine, liver, and adrenal glands, where they act locally in a paracrine or intracrine manner [27,29]. In a study investigating the source of elevated estrogen after menopause, an increase in the expression of aromatase (the enzyme catalyzing estrogen biosynthesis) was detected in the subcutaneous abdominal adipose tissue of ovariectomized rats [30]. This finding coincides with another study, which concluded that the conversion of androstenedione to estrogen was higher in obese women [31]. Additionally, a cross-sectional study on postmenopausal women found a link between rising body mass index and circulating estrogens (E1 and E2) [32]. However, the contribution of extra-gonadal E2 biosynthesis in different organ systems to the systemic levels of sex hormones remains debatable.




2.2. Biosynthesis of estrogens

The biosynthesis of estrogen takes place through a series of reactions catalyzed by a number of cytochrome P450 enzymes and different hydroxysteroid dehydrogenases [33]. It starts by the conversion of cholesterol to pregnenolone by cytochrome P450 cholesterol side-chain cleavage enzyme (CYP11A) [33]. Pregnenolone can either be converted to 17-hydroxypregnolone and consequently to dehydroepiandrosterone by 17α-hydroxylase (CYP17), or it can be converted to progesterone by3β-hydroxysteroid dehydrogenase (3β-HSD) [33]. Both dehydroepiandrosterone and progesterone are then converted to androstenedione by 3β-HSD and CYP17, respectively [33]. Afterwards, the androstenedione can be either converted to testosterone by 17β-hydroxysteroid dehydrogenase (17β-HSD), or to E1 by the aromatase enzyme (CYP19A1)[33]. Then, 17β-HSD catalyzes the conversion of E1 to E2 [33]. Fig. 1 demonstrates the steps of estrogen biosynthesis.




Fig. 1. The Biosynthesis of estrogens. Created by Chemdraw Software.

2.3. Estrogen receptors

Estrogens exhibit a wide range of physiological functions on different body tissues, including the cardiovascular, reproductive, skeletal, adipose, and central nervous systems [34–36]. E2 exerts its functions through acting on the estrogen receptors (ERα and ERβ) which are encoded by the ESR1 and ESR2 genes, respectively [37]. In addition, E2 also binds to a recently discovered G protein-coupled estrogen receptor1 (GPER1) or G protein-coupled receptor 30 (GPER30), also known as the membrane estrogen receptor [25]. Table 1 lists the gene and protein designations for estrogen receptors.

The expression of ERs has been identified in a wide range of cells and tissues. ERα is primarily found in the mammary glands, uterus, ovary (thecal cells), bones, male reproductive organs (testes and epididymis),prostate (stroma), liver, and adipose tissue [37,38]. ERβ is present in the prostate (epithelium), bladder, ovary (granulosa cells), colon, adipose tissue, and immune system [37,38]. In addition, both ERα and ERβ are markedly expressed in the cardiovascular and central nervous systems [37,38]. Within the cardiovascular system, ERα and ERβ are expressed in endothelial cells, vascular smooth muscle cells, and a variety of cardiac tissue, including cardiomyocytes, and cardiac fibroblasts [18,28].Stained human renal biopsies showed that ERα is mainly expressed the renal glomeruli and tubules [39], while both ERα and ERβ are expressed in the kidney proximal tubule [40]. According to several studies on rodents and humans, GPER1 is ubiquitously expressed within the reproductive system [41], cardiovascular system [42], renal system[43], brain [44], adrenal glands [45], adipocytes [46], and bones [47]




3. Aromatase enzyme

The aromatase enzyme, alternatively known as estrogen synthase, is a mono-oxygenase that belongs to the cytochrome P450 family and is encoded by the CYP19A1 gene [33]. This enzyme catalyzes the demethylation of carbon 19 in androgens causing their aromatization into18-carbon estrogens [110]. Androstenedione, testosterone, and16-hydroxytestosterone are the physiological substrates of aromatase, which are then transformed into E1, E2, and E3, respectively [111]. Collectively, the synthesis of estrogen is catalyzed by the aromatase enzyme, which converts endogenous androgens into estrogens [111]




3.1. The mechanism of aromatization

The aromatization process advances through a number of steps elaborated in Fig. 3. First, the methyl group at C19 in androstenedione is hydroxylated to produce 19-hydroxyandrostenedione, which is then followed by a second hydroxylation reaction to produce 19-dihydroxyandrostenedione [112,113]. The latter is then dehydrated to 19-oxoandrostenedione [112,113]. Finally, the steroid ring-A is subjected to oxidative cleavage of the C10-C19 bond followed by release of formic acid, leading to the formation of estrogen [112,113].




3.2. Distribution of aromatase

Estrogens are produced by gonadal and extragonadal sites. Gonadally and extra-gonadally-driven estrogens share the same chemical structure and biological activity, but differ in their metabolic pathways of synthesis [29]. Extra-gonadal estrogens are produced when C19 precursors are supplied to any tissue that expresses aromatase [29].Noteworthy, aromatase is primarily produced by ovarian granulosa cells in premenopausal women and adipose cells in postmenopausal women [114]

On the gonadal level, aromatase is expressed in both ovaries and testis. In the ovaries, aromatase expression is limited to differentiated preovulatory granulosa cells and luteal cells, and it is not expressed by undifferentiated granulosa cells in preantral follicles [115]. The follicle-stimulating hormone stimulates the growth and maturation of preantral follicles to the preovulatory stage, and the differentiation of granulosa cells, inducing the activation of aromatase [115]. Aromatase is downregulated after ovulation as granulosa cells develop into luteal cells [115]. Meanwhile, the detection of high amounts of estrogens in the male semen can be explained by the expression of aromatase indifferent testicular cells. Carreau et al. reported the presence of physiologically active aromatase in Leydig cells, Sertoli cells, spermatocytes, spermatids, and ejaculated spermatozoa in males [116].

Aromatase is also highly expressed in the placenta of both human and non-human primates [117], as well as other extra-gonadal tissues including the thalamus, hypothalamus, and hippocampus, indicating that aromatase is expressed widely in numerous regions of human brain in both men and women [118]. Aromatase activity has also been reported in stromal cells and adipocytes [119]. In bone tissue, aromatase has been identified within the human fetal osteoblastic cell line (SV-HFO) [120], and human osteoblasts [121]. The human hepatocellular carcinoma cells and HepG2 hepatoma cells showed increase in estrogen biosynthesis upon treatment with androgen precursors such as testosterone or androstenedione, indicating elevated aromatase activity [122]. Western blotting and immunohistochemistry showed that aromatase is expressed in the adrenal cortex as well as in adrenocortical tumors [123,124]. In addition, aromatase activity was demonstrated by 3[H2O] assay and gas chromatography-mass spectrometry in the parietal cells of the gastric mucosa [125]. It has also been previously reported that aromatase is expressed in epidermal keratinocytes and dermal fibroblasts [126,127]. In situ, hybridization revealed the presence of aromatase in human vascular smooth muscle cells but not in endothelial cells [128]. In men, aromatase is also expressed in the prostate [129]. Although extra-gonadal estrogen is synthesized in small amounts, its concentration is high enough to exert a biological effect locally [29]. Therefore, the disruption of aromatase homeostasis, accompanied by a disturbance in estrogen levels, will result in organ-specific effects.




3.3. Disruption of aromatase homeostasis

Both high and low levels of aromatase, and consequently high and low levels of estrogen, can cause a wide range of diseases and side effects [130]. Aromatase or estrogen excess-driven pathologies include breast, prostate, lung, gastric, and hepatic cancers, polycystic ovary syndrome,endometriosis, obesity, short stature, male hypogonadism, gynecomastia, and testicular hypertrophy [130–132]. Aromatase or estrogen deficiency-induced pathologies include cardiovascular problems [36,133], osteoporosis [36,130], hot flushes [134], vaginal dryness andvaginal atrophy [134], skin ageing, thinning and pigmentation [135,136], schizophrenia [130], Alzheimer’s disease [130], depression [137],insomnia [134], neuropathies [36], and elevated aldosterone levels [138,139]. Fig. 4 illustrates the sites of aromatase expression and estrogen disturbance-related effects.




Fig. 4. The major sites of aromatase and the associated estrogen-disruption pathologies. (-) estrogen deficiency, (þ) estrogen surplus. Created in BioRender.com

3.4. Regulation of aromatase enzyme

Aromatase enzyme is highly expressed in the ovarian granulosa cells [140]. The expression of aromatase is mainly induced by the follicle stimulating hormone which activates the transcription factor GATA4 that afterward activates other kinases, including ERK1/2, PKA, and PI3K [141]. Cyclic adenosine monophosphate (cAMP) is also involved in the transcription of aromatase [142]. In addition, it has been shown that the transcription of cardiac aromatase was stimulated by the administration of E2 therapy that can bind to ER to form a dimer which translocate into the nucleus where it can bind directly to the estrogen responsive element.

 

[CKO]

Wow this got technical quick. In my experience nandrolone increases synovial fluid which lubricates the joints. I can't say it heals the joint, but from what I remember in anatomy and physiology class, synovial fluid is the primary carrier of nutrients needed for joint health. An increase in fluid should reduce wear and tear and potentially increase the condition for joint health.

That being said, oxandrolone is shown to repair all sorts of tissues in the body, including joints. It also dries you out, so that is not great for joints. I've found it actually relieved arthritis in my shoulder for more than 6 months after discontinuation. The symptoms of arthritis with discontinuing nandrolone came back within 3-4 weeks. I had to increase hcg to counter the drying effect of oxandrolone.

I like both compounds. Nandrolone best attributes (imo) is its anti-inflammatory benefit. Oxandrolone is great for healing and nutrition uptake (see studies of alcoholics using it), it also messes with your mood less.