Growth Hormone

Growth hormone (GH) is a peptide hormone that is synthesized and released by somatotroph cells in the pars distalis of the pituitary gland. It belongs to a family of hormones known as the growth hormone family. This also includes prolactin (PRL) and placental lactogen. Despite the obvious differences in function, these hormones share a very similar structure. Likewise, GH and PRL are the only two non-tropic hormones synthesized and released from the anterior pituitary gland.

The synthesis and release of GH is directly regulated through its two hypophysiotropic hormones, growth hormone releasing hormone (GHRH) and growth hormone inhibiting hormone (GHIH, or somatostatin). Despite the direct regulation by these hormones, other hormones can affect the secretion of GH. Thyroid hormones are shown to have a direct effect on GH synthesis, ghrelin through the activation of the growth hormone secretatgoguge receptor (GHSR), and much like PRL, GH synthesis is directly downregulated by dopamine and dopamine agonists such as bromocriptine.

GHRH is synthesized in the arcuate and ventromedial nuclei of the hypothalamus while GHIH is primarily synthesized in the anterior periventricular region of the hypothalamus. These two hormones are in constant flux. Both hormones act on their respective receptors on the surface of somatotroph cells, where they activate second messenger systems that affect gene expression and calcium concentrations. When GHRH binds, GH gene expression is activated and intracellular levels of calcium increase to stimulate the exocytosis of GH. When GHIH binds, the inverse happens as a result of inhibitory G proteins on the receptor that fail to activate adenylate cyclase.

GH is naturally released in a pulsatile manner. This means that release of GH occurs in short bursts throughout the day rather than a constant release. Over half of our natural GH release occurs during deep sleep during stages 3 and 4. As we age and GH levels decline, it is a direct effect lower concentrations during these bursts rather than a decline in the number of bursts themselves. Because of this pulsatile manner, the detection of GH in the blood is not conclusive, and typically insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) levels are checked as they are kept more constant and their existence is a direct result of GH stimulation.

While GH does have independent effects in the body, majority of the effects are a result of IGF-1 activity. During adolescence, GH will have direct growth-promoting actions on progenitor and stem cells. Specifically, prechondrocytes in epiphyseal plates of long bone which induce longitudinal growth and satellite cells of skeletal muscle which induce myocyte differentiation. This occurs due to GH stimulating these cells to synthesize IGF-1 which has an autocrine and paracrine mitogenic effect, causing the progenitor cells and nearby cells to undergo mitosis.

IGF-1

As mentioned early, IGF-1 is a mitogenic agent that mediates the intended effects of GH. This peptide hormone is produced by many of the cells in the body, but the majority is synthesized in the liver. Most IGF-1 in blood is bound to IGFBP3 and very little circulates freely. Because of this, IGF-1 has no role in blood glucose regulation like its name might suggest.

Growth Hormone Secretagogues

GHSs are drugs that act as an agonist for the GHRH receptor and the growth hormone secretagogue receptor (GHSR). Endogenously, ghrelin is the primary ligand for GHSRs and they can increase the synthesis of GHRH. The two most prominent GHSs in bodybuilding would be CJC-1295 and GHRP-6.

• CJC-1295: CJC-1295 is a GHRH receptor agonist. Despite promising results in the increase of IGF-1, clinical trials were disrupted by the death of a participant.

• GHRP-6: GHRP-6 is a GHSR agonist. GHRP-6 is said to mimic the effects of ghrelin. Unfortunately, ghrelin has been recently linked to the proliferation of many different types of cancer through signaling action of GHSR.

Regulation

• Stimulation: Stimulation of GH, or more specifically GHRH, is typically induced by low blood glucose levels. Overall, GH is a glucose-sparing hormone, similar in sense to epinephrine and cortisol. Because of this, physiological and emotional stress can increase GH secretion. Many pharmacological agents are shown to stimulate GH secretion as well, including L-dopa, clonidine, propanolol, glucagon, insulin, and arginine.

• Inhibition: Like most hormones, GH operates under a negative feedback mechanism. Both high levels of GH and IGF-1 will inhibit GHRH.

Effects

Despite IGF-1 mediating many of the effects of GH, GH will also independently impact the same effectors. GH will induce lipolysis in adipocytes via activation of hormone-sensitive lipase, similar to epinephrine and cortisol. GH will also act in an antagonistic manner towards insulin. Most notably, GH has been shown to inhibit glucose uptake in muscle and bone. This is due to GH inhibit the Akt kinase phosphorylation that is necessary for insulin-mediated Glut-4 translocation. Essentially, GH will inhibit insulin from shuttling glucose into muscle. Similarly, GH will stimulate hepatic gluconeogenesis. Due to these major glucose-sparing effects and inhibition of Glut-4 translocation, GH is referred to as a diabetogenic hormone. Development of type II diabetes is common amongst patients with excessive GH levels and this places bodybuilders at risk, especially when utilized with insulin.

There have been different studies that state that GH either increases or decreases SHBG levels, however it has been confirmed that exogenous GH usage does not impact SHBG or free androgen levels. GH users may experience an increase in appositional bone growth, specifically in flat bone. This occurrence is known as Acromegaly. Joint pain and carpal tunnel syndrome are also common in those with high GH levels. A possible link to Hodgkin’s lymphoma is also being investigated.

Aromatase

Aromatase is an enzyme that converts testosterone to estradiol and androstenedione to estrone. Similarly, 17-ketosteroid reductase is an enzyme that is capable of converting androstenedione to testosterone and estrone to estradiol. Aromatase is named based upon the fact that it removes a methyl group on the 19th carbon and rearranges ring A into an aromatic ring, hence it aromatizes the testosterone molecule.

Aromatase is found in many different cells in the body, however it is primarily found in adipose tissue. The liver, skin, and testes are also primary sites of aromatization. In the testes, you have two different cells that respond to the gondaotropic hormones (LH and FSH). Leydig/interstitial cells respond to LH and initiate the synthesis of testosterone. Sertoli/sustentacular cells respond to FSH and initiate and support spermatogenesis. Sertoli cells do not produce testosterone but they contain FSH-dependent aromatase. The estradiol produced in Sertoli cells binds to E2 receptors in Leydig cells and the estradiol will suppress the Leydig cell’s response to LH stimulation. Aromatase activity in other cells are not FSH-dependent. Much of the brain contains aromatase, except the pituitary gland.

Aromatase Regulation

Aromatase is decreased endogenously by prolactin and anti-Mullerian hormone, although AMH is irrelevant and concentrations are almost non-existent in adult males. It is also decreased exogenously by aromatase inhibitors, nicotine, zinc, vitamin E, and resveratrol. The enzyme is increased endogenously by gonadotropins, insulin, testosterone, and androstenedione. Increased adipose tissue increases quantity of aromatase in body.

Aromatase Inhibitors

Aromatase inhibitors (AIs) are medications that are primarily used in the treatment of breast cancer and gynecomastia. AIs inhibit the action of aromatase through competitive inhibition. AIs will bind either reversibly or irreversibly to the active site of aromatase, blocking the binding of testosterone and androstenedione. There are two types of AIs: type I steroidal and type II non-steroidal. Type I AIs bind irreversibly since they are steroid-based and will act as a false substrate for aromatase. Type II AIs bind reversibly by temporary interference with aromatase’s heme group.

Another classification of AIs are generational. First generation AIs like aminoglutethimide inhibited other steroidogenic pathways, reducing glucocorticoid, mineralocorticoid, and thyroid hormone synthesis in the process. These AIs also have a tendency to increase hepatic enzymes. Second generation AIs like fadrozole and formestane are shown to also inhibit the steroidogenic pathway of aldosterone. Currently, third generation AIs are the preferred type since they do not affect steroidogenesis of other steroids. There are three main third generation AIs:

• Letrozole: Letrozole is a type II non-steroidal AI, so it will bind reversibly. It is shown to have the highest potency of any AI, operating at a 99% degree of potency based off of the degree of inhibition of total body aromatase.

• Anastrozole: Anastrozole is a type II AI with a 96% degree of potency.

• Exemestane: Exemestane is a type I steroidal AI, and is the only third generation AI that is type I. Because of this, it will bind irreversibly to aromatase, an action often referred to as suicide inhibition.

Selective Estrogen Receptor Modulators

SERMs are therapeutic agents that shows selectivity of action on estrogen receptors. Can act as antagonist to ERs in bone, liver, and heart. Can act as antagonist to ERs in brain and breast tissue. This can provide the beneficial effects of estrogen in certain tissues while inhibiting the deleterious effects of estrogen in others. There are two distinct estrogen receptors: ER-alpha found primarily in breast tissue and ER-beta found pretty much everywhere else in the body. This selectivity is achieved by the SERMs ability to recruit co-repressors and co-activators (to act as antagonists and agonists, respectively) that can regulate gene expression normally induced by ER activation.

• Tamoxifen: Tamoxifen acts as an antagonist in breast tissue and agonist in bone. Inhibition of ER receptors in breast tissue has shown to reduce pubertal gynecomastia. It can have a paradoxical effect on hepatic ERs have can affect lipid metabolism which can lead to elevated triglyceride levels. Prolonged use has a hepatotoxic effect. This effect has been implicated in pancreatitis. Tamoxifen has also been shown to cause hepatic steatosis (fatty liver disease) as a result of increase uptake of triglycerides in hepatocytes.

• Clomifene: Clomifene acts as an antagonist in the hypothalamus. Typically, estradiol binding to ER receptors in the hypothalamus leads to negative feedback inhibition of gonadotropins LH and FSH. Inhibition is shown to increase gonadotropin synthesis. This is why clomifene is recommended as an LH agonist in post-cycle therapy protocols. Because of this effect, clomifene’s intended use is as an ovulation inducer. Clomifene is also used as an off-label replacement for TRT in hypogonadotropic hypogonadic men with fertility concerns since it will not suppress LH and FSH levels. Most common side effect is visual issues. Much like tamoxifen, clomifene can cause hyperlipidemia and hepatic steatosis.

• Raloxifene: Like tamoxifen, raloxifene acts as an antagonist in breast tissue and agonist in bone. Intended use is to prevent osteoporosis in postmenopausal. Effects and method of action are similar to tamoxifen.

Other Anti-Estrogens

• Epitiostanol/Methylepitiostanol: Epitiostanol is only bioavailable via injection, however a methylated version marketed as Epistane is able to survive first-pass metabolism. This drug acts as estrogen receptor antagonist and as a weak androgen receptor agonist. Utilized as a steroidal breast cancer therapy in Japan.

• Drostanolone: Drostanolone is a DHT-derived steroid hormone that is utilized as an anti-estrogenic drug to treat breast cancer. This is the preferred androgen used in the treatment of breast cancer due to the fact it has a low androgenic profile and has a minimal virilizing effect on women.

• Selective Estrogen Receptor Degraders: SERDs are similar to SERMs, but only act as antagonist to all ERs. Fulvestrant is the most common, however, I have not heard about a practical use as a PED.

Steroids and Acne

Unfortunately, any amount of steroids is going to increase acne if you are predisposed to it. Some hormones will affect people differently, some get more acne on tren, some test, some NPP, etc. Regardless of E2, you will get acne from steroids.

EstrogenE2 high or low can both cause acne, and acne may result even from having normal estrogen levels just due to the androgens in your system. Aim for consistent E2 levels, this will lower your chance of acne the most.

DHT and acne

I’ve used nizoral before and had a similar effect with head and shoulders (which apparently works on fungal acne, do not know how to identify it though.)

Ketoconazole or Nizoral are typical anti androgens. Get the benefits of stopping DHT from binding to the sebaceous gland without ingesting an anti-androgen.

Lifestyle habits and washing habits for Acne

Firstly, a great resource is acne.org and it’s subsequent forums and this includes much general consensus from acne groups.

Refrain from using harsh washes or activities that will increase inflammation of the skin (#1 reason for acne). This means:

• Do not use alcohol, sulfates (soap), acne bead scrubs, overly drying washes. instead use gentle cleansers, (acne.org has one), sulfate free, and wash your face very lightly and splash water to wash it off. PAT to dry DO NOT scrub.

• Do not touch, scrape, or pop your acne. Don’t run your dirty fingers over your acne. Do not spend time pushing out plugged comedones, black heads, white heads. Do not excessively press and pop pimples that are not popping, even if the end result it pops. If it takes more than 15 seconds for it to pop, leave it alone until its ready instead: if you must, only pop pimples that are easily popped and ready with clean hands right before you wash it. A warm shower can make it easier to pop but scalding hot water may be negative to skin moisture. However it is more ideal to never pop pimples

• Do not sleep on dirty bedsheets or pillow cases. Do not re wear dirty shirts, or continue wearing a gym shirt that you just worked out in. instead, shower/rinse immediately after gym and put on a clean shirt. If you go home after gym and shower that is usually fine too. Replace bedsheets 2x a week and pillow cases EOD (flipping the pillow after the day to get double use)

• Do not excessively wash your skin, it leads to overdrying. If possible, wash your back/face with a gentle wash 1x a day at the max. If you need to take a second shower before bed due to general day sweat, rinsing with water and wiping with hands is completely fine.

Washing

• As counterintuitive as it sounds, over washing can lead to acne. Your aim should be to maintain a certain level of stability with your skin. This means overwashing will dry out your skin and cause acne. You must completely avoid normal soap and sulfates.

• Consider a salicylic acid wash or benzoyl peroxide wash (the OG proactive uses this) and using 1x a day max. If they dry out your skin stop for a couple days. Some people find success with a benzoyl peroxide wash, but I think salicylic acid is better as benzoyl peroxide is a generally better treatment for leaving on skin. Others have the opposite opinion.

• Consider washing your back with no soap at all if you haven’t gotten extremely dirty. Your body maintains a natural ph and good bacteria that lessen the ability for bad bacteria to colonize and from acne. Simply rinsing off and not washing at all can do wonders due to the reduced inflammation on your skin.

• Wash lightly, do not scrub, do not rub hard. Your objective is to clear the previous medicine from your skin and remove any layer of acne promoting containment on your skin. (Bacteria from sweat, pollution, clogged pores, etc.)

Treatment

This is where it gets to the good stuff. I’m so fucking surprised barely anyone here knows about the best treatments for actually removing acne.

Test all medications first in a small part of skin before dousing yourself with it. BP, azaelic acid tend to be the biggest culprits of redness and differin to a lesser extent.

• Benzoyl Peroxide 2.5% (gel version is best) – there is no evidence that stronger concentrations are better, and they generally just dry out the skin more. Benzoyl Peroxide is the holy grail of treatment because bacteria never get resistant to it. It provides an oxygen rich environment that is impossible for bacteria to live in. Issues with BP = sensitivity to sunlight, redness on skin, allergic reaction (under 5% have this) so take away = start slow when using benzoyl peroxide, EOD at first, then ED. 2x a day if your body can handle it. It also bleaches clothes, so if you put it on before putting on clothes you need to let it dry, and probably have a white t shirt/white sheets.

• Adapalene (brand name Differin) is a 3rd generation retinoid that specifically targets the mechanisms that produce acne. It prevents the formation of comedones by 50-60% according to studies. Retinoids are structurally related to Vitamin A – and accutane is a retinoid. Differin is a topical retinoid and since being applied to the skin it does not absorb through the blood stream (as shown by studies significantly insignificant amounts get through). So, you’re basically taking topical accutane. Differin has always been the most effective acne medication for me in permenantly reducing the amount of acne I get, and after a year of diligent use in my teens I never got pimples anymore. Additionally, Adapalene increases the efficacy of other popular acne treatments such as topical clindamycin and benzoyl peroxide.

• Topical clindamycin: clindamycin is a popular antibiotic, but when used topically for acne treatment it significantly boosts the efficacy of adapalene and benzoyl peroxide. However, tolerance increases pretty quickly, and I only recommend using it when a breakout occurs, or for spot treatment of specific pimples. It’s useful l usually sold in combination with benzoyl peroxide 5% but it’s in your interest to get it separately because 5% BP is over drying and this way you can regulate your tolerance to it

• Curology (prescription) 4% azelaic acid . (precursor to salicylic acid) 1% clindamycin, 4% nicotinamide. I’ve read good things about this from skin care addiction but have not used myself. Studies show nicotinamide being as effective as 1% clindamycin without resistance.

• Salicylic acid option: a slightly weaker option than benzoyl peroxide, but still effective. Be sure the lotion it’s mixed with is quality and you might find something useful. You might be better off finding it in pure gel. However BP has shown in studies be more effective and the combo treatment with differin is promising.

• Jojoba oil: widely considered the best type of oil to moisturize your skin because it is very similar to the natural oils that we produce. It’s a favorite on /r/skincareaddiction

zinc 20-50mg for 3 days after breakout you can’t stay on high zinc forever but I do this when I get a breakout and it’s pretty effective. Lots of anti inflammatory properties in zinc. 10-20mg is about a maintainece dose. I like to use zinc-carnosine complex because it has the added benefit of restoring stomach lining and reversing damage from spicy food etc. No heartburn since using it.

Adapalene is prescription only, but should be over the counter soon. it also comes in a mixture formula with BP called epiduo

Clindamycin is prescription as well. Benzoyl peroxide can be found anywhere. For all of these drugs you should be aiming to get the gel versions. If you go to yourdermatologist and ask for them you should probably be able to get everything that you want.

Adapalene (used first) followed by clindamycin, and benzoyl peroxide, is the holy trinity of destroying acne. If using these 3 medications is causing you to get overly dry skin, you probably want to drop everything but always continue adapalene usage as it improves your skin over time and reduces your ability to create new comedones. If you can only take adapalene 1x a day is fine. 2x is better. It’s better to use a thin layer of it everywhere (more just overdries) if your skin is sensitive from overuse, just spot treat with it for a while but you really want to throw it on everywhere

Moisturizing

Use a non-comodegenic moisturizer. The oil you should be using on your face in my opinion is jojoba oil. Cetaphil and CeraVe make great facial moisturizers. Use these after treatment in combination with jojoba if jojoba oil is not enough.

Dietary Factors

• Many people swear that cutting out dairy reduced their acne. Considering the amount of hormone derivatives pumped into cows, it is a reasonable assumption. Since many of us are putting hormones into our body anyways, it might not matter, but most people get reduced acne from cutting out Dairy.

• Cutting out Sugar & Fructose can reduce acne. Inconsistent blood sugar levels are related to acne, and high amounts of sugar provide a good environment for bacteria to proliferate. Try it out.

• Eating more veggies. Try it out, fuck it, it might help.

Generally diet cannot cure acne on its own, but if it helps, it’s worth it. If something you’re eating is creating acne, it’s probably not something you want in your body anyway.

Hope you guys enjoyed this post, if you get anything out of it: GET ADAPALENE! it’s the most effective treatment for preventing further acne (and reducing current). It’s basically topical accutane.