LGD-4033 is a selective androgen receptor modulator (SARM) currently being researched for its potential applications in the clinical treatment of muscle wasting, osteoporosis and other related conditions.
LGD-4033 is purported to be the most potent SARM currently in clinical trials, with its data exhibiting the most favorable ratio of anabolic activity relative to androgenic activity.
What Is LGD-4033?
LGD-4033, also known as Ligandrol, was originally developed by Ligand Pharmaceuticals, Inc. and was licensed afterwards to Viking Therapeutics.
It is now officially named VK5211 under Viking Therapeutics.
LGD-4033 is a selective androgen receptor modulator (SARM) developed to be a potential treatment for a variety of musculoskeletal degenerative diseases.
The main goal of all SARMs essentially boils down to finding the right compound that provides the same therapeutic benefits of testosterone with improved safety, tolerability and patient acceptance.
So far, LGD-4033 has demonstrated an incredible efficacy profile, and the clinical data suggests it could be a best-in-class small molecule SARM.
LGD-4033 Potential Clinical Applications
Despite being the endogenous hormone that men naturally produce, Testosterone use in a clinical setting for treating muscle and bone wasting diseases is extremely limited because of its androgenicity and pharmacokinetic issues.
Testosterone is not selective enough for muscle tissue and bone relative to other androgen affected tissues like the prostate, and is not orally bioavailable [R].
This is why a SARM like LGD-4033 is so promising, as it is non-steroidal, extremely selective, and exhibits a high level of bioavailability [R].
Testosterone exhibits a 2:1 selectivity for muscle to prostate [R].
In men, treatment with testosterone and other anabolic androgenic steroids (AAS) could result in prostate growth stimulation and artificially induce hypogonadism, hence why a more selective treatment that can target muscle tissue and bone specifically would be a more desirable alternative [R].
In women, treatment with testosterone or other AAS can lead to the development of male gender characteristics (virilization), hence why a more selective treatment that is capable of fulfilling the same functions of androgens would be a more desirable alternative [R].
Testosterone induces significant androgenic activity at therapeutic dosages which disqualifies it entirely as an optimal treatment for muscle and bone wasting diseases.
This is why SARMs like Ligandrol may prove to be safer, more effective alternatives [R].
The ideal anabolic agent should demonstrate anabolic selectivity in muscle and bone without suppressing luteinizing hormone (LH), not negatively interact with other steroid receptors in the body, exhibit a high level of oral bioavailability without being 17 alpha-alkylated, and avoid 5-alpha reduction to DHT and aromatization into Estrogen [R].
SARMs were first discovered in 1998, following which several different compounds were developed by a variety of pharmaceutical companies in order to find a viable compound to satisfy this obvious need in degenerative disease treatment [R].
Mechanism Of Action
LGD-4033 has a high level of bioavailability, meaning it can be dosed orally as opposed to requiring intramuscular injection, as is the case with most traditional anabolic steroids.
It also does not require 17 alpha-alkylation in order to be absorbed and utilized in the body, as opposed to 17 alpha-alkylated oral anabolic steroids that are intentionally designed to be liver toxic with a methyl or ethyl group at the C17α position so they are orally bioavailable.
SARMs, like LGD-4033, stimulate androgen receptors in a selective way, whereby they induce a significantly greater amount of anabolic activity in the body relative to androgenic activity [R].
LGD-4033 binds to the androgen receptor with an extremely high affinity (Ki of ~1 nM) and selectivity, and once it does this it exerts anabolic effects in muscle tissue and bone.
Due to the tissue-selective mechanism of action and oral route of administration, Ligandrol may be effective at producing all of the therapeutic benefits of testosterone with a vastly improved safety profile.
The negative effects that stem from traditionally used anabolic steroids converting to 5α-reduced androgens that can increase the risk of benign prostate hyperplasia, prostate carcinoma, acne breakouts, and substantially expedited male pattern baldness could potentially be averted entirely if LGD-4033 became an approved treatment alternative in a clinical setting.
LGD-4033 could potentially provide a sufficient amount of anabolic stimulation to completely mitigate muscle wasting and bone degradation, while simultaneously avoiding the occurrence of androgenic side effects in women entirely.
The lack of androgenicity is favorable for both men and women, but it proves especially useful in the context of treating women, as even low dosages of anabolic androgenic steroids would induce virilization.
Finding a balance between a therapeutic amount of anabolic activity with a near complete absence of androgenic activity is extremely difficult to integrate into an anabolic agent, but the clinical data suggests that Ligandrol may be capable of achieving just that.
After binding to the androgen receptor, LGD-4033 blatantly exhibits the ability to increase muscle mass and strength, and it is also reported to increase bone formation, bone strength and decrease bone resorption [R].
Aside from Ostarine, LGD-4033 is the closest SARM to making it through clinical trials and being approved.
LGD-4033 Clinical Trials
LGD-4033 has undergone extensive testing in a number of preclinical animal models.
Preclinical Rat Models
The data revealed a greater than 500-fold selectivity of muscle tissue to prostate in rats.
A greater than 500:1 anabolic to androgenic selectivity would make LGD-4033 the most selective SARM to date, even more so than BMS-564,929, which has a selectivity of 160:1, and may have had its overall potency in muscle tissue exaggerated in its preclinical findings [R].
In the preclinical studies castrated rats that were given LGD-4033 experienced increased muscle size, and in a rat model of osteoporosis, the rats experienced increased bone mineral density.
To exhibit tissue selectivity in rats, they were castrated and left untreated for 14 days to provide ample time for muscle and prostate atrophy.
Following which, the rats were administered varying dosages of LGD-4033 for the next 14 days.
The following graph illustrates the data derived from the preclinical studies which exhibits how much LGD-4033 stimulated muscle growth relative to prostate growth in comparison to Testosterone.
According to Viking, Testosterone shows no tissue selectivity in the data, which isn't exactly true, as it does exhibit a 2:1 selectivity up to a certain point.
Any anabolic agent will become more androgenic:anabolic the higher the dosages are pushed, as a diminishing returns effect sets in with the anabolic component.
The goal of SARMs is simply to replicate the therapeutic benefits of Testosterone though, not to create a super hormone that can dose dependently build muscle with limitless capabilities while simultaneously having 0 androgenic effects at all dosages, as that would be unreasonable and impossible to develop (for now).
LGD-4033 stacked up against Testosterone very well in the preclinical models with a greater than 500x tissue selectivity of muscle to prostate.
In the preclinical rat model of osteoporosis, ovariectomized female rats were allowed to develop osteopenia for eight weeks before once-daily oral treatment with LGD-4033 for 12 weeks.
LGD-4033 successfully increased lumbar spine bone mineral density as effectively as Estradiol and Testosterone (graph on the left), and also significantly decreased trabecular bone turnover compared to placebo (graph on the right).
Preclinical Primate Model
In a preclinical primate model, Cynomolgus monkeys were orally administered Ligandrol once per day at dosages of 0, 0.6, 3, 15, or 75 mg/kg for 13 weeks.
Ligandrol treatment resulted in a dramatic increase in lean muscle mass compared to the placebo group.
The results showed a significant increase in body weight in both male and female monkeys during the study.
Body weight increase was measured in % gained (y-axis of the graphs).
After 13 weeks of once per day dosing, there was a significant increase in body weight for all monkeys except the untreated group.
The 75 mg/kg dosing was stopped after 48 days due to signs of toxicity.
This isn't very relevant to Viking's Phase 2 clinical trial though, as human dosages did not exceed 2 mg per day.
More than than 70% of the mass gained was retained after a four-week recovery period when the weight of the monkeys was checked again.
The preclinical data suggests that Ligandrol is highly selective for muscle tissue, and could potentially perform with a much improved therapeutic profile in a clinical setting relative to testosterone.
Three Phase 1 studies on LGD-4033 were successfully accomplished.
The Phase 1 trials are the first stage of testing in human subjects designed to assess safety, side effects, best dosage, and formulation method for the drug.
The takeaway from all Phase 1 human trials was that LGD-4033 exhibits a very encouraging safety profile and tolerability at dosages that provide significant improvements in lean muscle mass, and positive trends in strength and performance measurements.
Single Ascending Dose Study
The first Phase 1 trial involving LGD-4033 was a randomized, double blind, placebo controlled trial conducted in 2009 on 48 healthy male volunteers.
The volunteers were divided into six cohorts and received an escalating daily dosage of LGD-4033 ranging from 0.1 mg per day to 22 mg per day.
All doses of LGD-4033 tested in humans (even the 22 mg per day dosage) were shown to be safe and well-tolerated, with predictable pharmacokinetics.
The pharmacodynamics results showed dose-dependent reductions in total serum testosterone levels, sex-hormone binding protein (SHBG), and fasting serum HDL, which is consistent with the mechanism of action of SARMs (and all anabolic agents).
21 Day Multiple Ascending Dose Study In Healthy Young Men
The second Phase 1 trial involving LGD-4033 was a placebo-controlled study conducted on 76 healthy men (21–50 years).
They were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days.
Blood counts, chemistries, lipids, prostate-specific antigen, electrocardiogram, hormones, lean and fat mass, and muscle strength were measured during and for 5 weeks after intervention.
LGD-4033 was shown to be safe and well-tolerated [R].
There was a dose-dependent suppression of total testosterone, SHBG, HDL cholesterol and triglyceride levels.
FSH and free testosterone only showed significant suppression at the 1 mg per day dosage.
Lean muscle mass increased significantly in a dose dependent manner, with minimal changes in fat mass [R].
Hormone and lipid profiles all returned to baseline after treatment discontinuation.
There were no drug related serious adverse events, no liver toxicity, no negative effect on electrocardiogram results, and no adverse effects on Prostate-Specific Antigen (PSA) levels [R].
There was a dose proportional increase in drug concentration on days 1 and 21, suggesting that accumulation occurs upon multiple dosing, which is very important to note.
If someone took the same dose every 24 hours, LGD-4033 would eventually accumulate to extremely high levels in the blood.
It would be wiser to assume the half life is closer to 36 hours based on the clinical data in this study.
LGD-4033 increased lean body mass on average 1.21 kg (2.67 pounds) at the 1 mg dosage [R].
The increase in lean body mass was dose-dependent, and can be assumed will increase more as the dosage increases.
The capability of LGD-4033 to increase lean muscle mass in such a short time span without negatively affecting PSA levels bolds well for its efficacy and safety profile moving forward.
7 Day Study In Elderly Men And Women
The third Phase 1 trial involving LGD-4033 was conducted to evaluate the safety, tolerability and pharmacokinetics properties of LGD-4033 in elderly subjects.
This study is assumed to be the most representative of the hip fracture population, which is the main clinical application Viking seeks approval for with LGD-4033.
The end goal is to receive approval to treat patients who have suffered a hip fracture by slowing or prevent the loss of their lean body mass or bone mineral density.
LGD-4033 had predictable pharmacokinetics (similar to those reported in younger male subjects) and was shown to be safe and well-tolerated at all doses evaluated with no serious adverse events observed.
In Phase 2, the scope of treatment applications for LGD-4033 narrows as there needs to be a specific condition that the SARM is meant to treat in order to receive approval.
In this trial, the efficacy and safety profile of LGD-4033 in the maintenance or improvement of lean body mass, bone mineral density, and function in patients recovering from non-elective hip fracture surgery is assessed.
Negative Changes In Body Composition Following A Hip Fracture
Hip fracture is associated with a number of morbidities, most of which are a consequence of lean muscle loss and bone degradation following hip fracture surgery.
Typically, healthy older females without hip fractures would only lose approximately 1% of their lean tissue per year and gain 1.7% body fat [R].
Bone mineral density also severely declines in hip fracture patients.
The negative changes in body composition following a hip fracture are represented in the following graphs [R].
The ability to slow or prevent the loss of lean body mass or bone mineral density would likely have a profound impact on patient recovery following hip fracture.
LGD-4033 Phase 2 Trial Results
The first LGD-4033 phase 2 trial started October 30th in 2015 and completed in March, 2018 [R].
The clinical trial was 12 weeks long and involved 108 patients (83 women and 25 men) who were at least 65 years old and had suffered a hip fracture within the past three to seven weeks.
Subjects were administered placebo, or 0.5 mg, 1.0 mg, or 2.0 mg of LGD-4033 once-daily for 12 weeks.
The primary goal of the trial was to assess changes in lean body mass, with secondary and exploratory endpoints including assessments of patient quality of life, functional status, change in appendicular lean mass, total lean body mass, bone mineral density and activities of daily living.
LGD-4033 produced significant increases in lean body mass and appendicular lean mass following 12 weeks of daily dosing in all subjects.
A consistent dose response was observed across all primary and secondary efficacy measures.
LGD-4033 exhibited encouraging safety and tolerability, and there were no drug-related serious adverse events in the study.
Is LGD-4033 As Strong As Steroids?
It is typically not a relevant comparison to make between Ligandrol and most steroids because the dosages that are compared are so much different.
For example, 10 mg of Equipoise (Boldenone) per day would not equate to nearly as much muscle growth as 10 mg of LGD-4033 per day.
I believe LGD-4033 is absolutely as potent of a muscle builder as moderate dosages of Primobolan, Turinabol, Boldenone, Anavar, and several other anabolic steroids.
I have yet to see data on a steroid exhibiting a lean muscle gain of 2.67 pounds using only 1 mg per day.
At therapeutic dosages, milligram for milligram LGD-4033 will outperform Anavar, Turinabol, Primobolan, Equipoise, and many other traditional anabolic steroids, with a favorable selectivity for anabolic:androgenic activity.
LGD-4033 is significantly more potent than many very well known testosterone analogs [R].
LGD-4033 Vs Nandrolone
In an assessment of change in lean body mass at 6 months in hip fracture patients, LGD-4033 significantly outperformed Nandrolone in muscle gain.
Nandrolone is one of the few anabolic steroids that was approved for clinical use in humans, and remains a very popular steroid for performance enhancement to this day.
More commonly known as “Deca” (Nandrolone with the Decanoate ester) or “NPP” (Nandrolone with the phenylpropionate ester).
LGD-4033 Vs Anavar
10 mg of LGD-4033 vastly outperforms Anavar in all efficacy measures.
Lean muscle gains and strength gains are significantly more pronounced with LGD-4033, and it is just as well tolerated by both men and women.
I personally know over 10 women who've tried both on separate occasions for performance enhancing purposes.
Every single one reported far better results from LGD-4033.
How LGD-4033 Compares To Other SARMs
LGD-4033 has a competitive effect on total lean body mass relative to other clinical-stage SARMs, and is more potent on muscle compared with myostatin-targeting approaches.
LGD-4033 Vs Ostarine
While Ostarine also has an encouraging efficacy profile and is clearly very selective for muscle tissue relative to prostate (and other androgen affected tissues), in comparison to LGD-4033 it is weaker in almost all facets.
Milligram:Milligram Ligandrol (VK5211) outperforms Ostarine (Enobosarm) with greater increases in lean muscle mass and strength.
However, Ostarine is less suppressive than LGD-4033, which can be important for recovering baseline hormone levels as quickly as possible after discontinuation.
LGD-4033 Vs RAD140 (Testolone)
RAD140 is commonly compared to LGD-4033 as a “bulking” compound.
RAD140 is reported to be a dryer compound, with the potential to increase strength even more so than LGD-4033.
Some individuals seem to respond better to one or the other, with impressive gains in strength being consistent with either of their use.
When it comes to hypertrophy, LGD-4033 seems to outperform RAD140 in most instances (not always the case), making it the candidate of choice for most for sheer lean muscle size gains.
It should be noted that RAD140 is still in the preclinical stage, meaning it had no current human trials to use as referential data, and those conclusions are drawn purely off of anecdotal logs.
Granted, there are thousands of anecdotal logs (on humans) now to reference, which are quite insightful, but they are certainly no replacement for approved clinical trials.
LGD-4033 Vs S23
S23 is a SARM in the preclinical stage being developed by GTx, Inc as a potential male hormonal contraceptive (the same company that created Ostarine).
It binds to the androgen receptor harder than its predecessors (like Andarine) and has an extremely potent effect in muscle, with a high level of selectivity.
Comparing LGD to S23 head to head there are many who would argue that S23 is the strongest SARM in development right now, and they could be right, however, its still in the preclinical stages, and it is extremely suppressive.
This is why it is being developed as a potential male contraceptive right now, it is far more suppressive than LGD-4033.
In the preclinical rat model, S23 suppressed LH levels by more than 50% after only 14 days with doses as low as 0.1 mg per day [R].
There are also reports of aggression with S23, as well as some strange side effects like dehydration and increased body temperature.
While some hardcore recreational biohackers may opt to experiment with S23 because of all of the positive anecdotal experiences that can be found online, LGD-4033 is the more promising SARM at the moment overall.
LGD-4033 Vs LGD-3303
LGD-3303 was hyped up as a superior alternative to LGD-4033, and in its preclinical model appeared to have some encouraging results.
While it appears to still be in the preclinical stage, it is unclear if any developments have taken place since that first study, as it was completed over a decade ago in 2008.
Anecdotally, LGD-4033 appears to be the candidate of choice among recreational users, with it consistently outperforming LGD-3303 mg:mg in lean muscle gains and strength gains.
Some users swear by the efficacy of LGD-3303, so it shouldn't be written off entirely, but there is simply an overwhelming amount more evidence to support LGD-4033 as the superior SARM of the two.
LGD-4033 Results (Anecdotal/Recreational Use)
As shown in the clinical trials, LGD-4033 can increase lean muscle mass by 2.67 pounds within three weeks (on average) in young men at a dosage of 1 mg per day [R].
Predictably, LGD-4033 became a popular addition to athlete's regimens who were seeking performance enhancement.
I have personally seen several very impressive transformations accomplished using only SARMs.
Gains upwards of 5-10 pounds of lean muscle mass are commonly reported among recreational users within a 4-8 week cycle.
LGD-4033 is often referred to as the best mass building SARM, as it seems to exhibit greater muscle building potential than all other first-generation SARMs.
Typically, it is incorporated into bulking phases where LGD-4033 is used to enhance strength and hypertrophy in conjunction with a calorie surplus.
Users report some water retention with Ligandrol usage, however, I believe that this has more to do with body composition, daily water/potassium/sodium intake, caloric intake, cardio regimen (or lack thereof), and overall diet choices.
However, predicting how much muscle an individual will gain from LGD-4033, or any anabolic agent for that matter, can vary wildly depending on a variety of factors.
Substantial increases in strength are commonplace among recreational users as well.
A handful of users have reported increases in strength of their flat barbell bench press, squat, and/or deadlift by as much as 100 pounds in a focused bulking phase.
If a diet comprised of enough macronutrients, micronutrients and overall calories is adhered to for the duration of a LGD-4033 cycle, anecdotal reports suggest that gains of muscle upwards of 10 pounds and strength gains of 50-100 pounds on compound exercises are realistic.
My LGD-4033 Review
I've used LGD-4033 a handful of times, and my experience was fairly consistent with other anecdotal reports, but to a much lesser extreme.
By the time I tried it, I already had several cycles of anabolic steroids under my belt, so I didn't expect it to really blow me away.
My experience is less useful to reference as my body is already above and beyond my genetic limit via years of previous anabolics usage, however, I do believe that of all the SARMs, I feel that LGD-4033 had the greatest overall effect with the best side effect profile for me personally.
I also didn't lose any hair from it, which to me is the number one draw of an anabolic agent.
Once more data comes out on Ligandrol, I may start titrating my TRT down a bit more and start incorporating it in some capacity into a long-term regimen, as opposed to the way I've used it to date which is in intermittent “blast” phases.
The only other compound I believe is formidable to LGD-4033 in regards to overall size and strength gains is S23, which is still in the preclinical stages and hasn't been trialed in humans yet.
Milligram : Milligram, LGD-4033 induces substantially more anabolic activity than any other viable SARM alternative, and even outperforms most anabolic steroids.
The first Phase 1 study conducted on LGD-4033 established safety and tolerability of LGD-4033 up to dosages of 22 mg per day in humans.
It is very unlikely that 22 mg per day will be necessary to replicate the anabolic properties of Testosterone to prevent the loss of lean muscle or bone mineral density in hip fracture patients, however, it is useful to know that it has established a fairly encouraging safety profile even at dosages as high as 22 mg.
LGD-4033 produced dose-dependent effects on primary and all secondary measures of lean body mass, with significant increases in lean body mass and appendicular lean mass following 12 weeks of daily dosing.
The highest dosage utilized in Phase 2 clinical trials was 2 mg per day for therapeutic purposes [R].
In a recreational capacity, it is quite common for men seeking performance enhancement to report using 10 – 20 mg of LGD-4033 per day, with women using 5 – 10 mg per day.
These dosages were determined by recreational users based upon anecdotal logs and personal experimentation, and are not concrete guidelines that dictate correct or incorrect use.
While LGD-4033 was generally regarded as safe in human trials using dosages as high as 22 mg per day, that doesn't mean it had no negative side effects.
These were some of the negative side effects reported in the clinical data, as well as anecdotally among recreational users.
Decreased Good Cholesterol (HDL)
The clinical data shows dose-dependent suppression of HDL cholesterol and triglyceride levels with LGD-4033 usage [R].
A negative effect on HDL levels is consistently noted as a common side effect of all traditional anabolic steroids, and other SARMs.
Despite SARMs ability to be selective about how they exert anabolic activity in the body, they evidently do not differ much from anabolic steroids in regards to their effects on lipid profiles.
SARMs have shown to suppress luteinizing hormone (LH) and follicle stimulating hormone (FSH) through the hypothalamus-pituitary-testis axis, thus decreasing testosterone in a dose-dependent manner [R].
Ligandrol suppressed Sex Hormone-Binding Globulin (SHBG) and total testosterone levels in clinical trials in a dose-dependent manner.
Serum free testosterone and FSH levels were only suppressed in the subjects treated with 1 mg of Ligandrol [R].
There was no LH suppression in subjects treated with Ligandrol during the 21 day clinical trial conducted on healthy young men.
However, the treated groups were only administered either 0.1 mg, 0.3 mg, or 1.0 mg for three weeks, which are relatively low dosages and is also a short time frame.
Based on the overwhelming supporting data on anabolic agents collected over the past 50 years, I believe it's safe to say that LGD-4033 will show blatant reductions in all of these hormone markers in a dose dependent manner, and the dosages in the studies just weren't high enough to consistently yield this data.
At higher dosages (above 1 mg), I am sure serum free testosterone levels would drop considerably as the dose was titrated up, and other markers would decrease in parallel.
Elevated Estrogen Or Decreased Estrogen
LGD-4033 does not aromatize into Estrogen, however, by suppressing natural Testosterone levels it can create an unfavorable balance between Testosterone and Estrogen in the body.
By occupying the androgen receptor with such a high affinity, LGD-4033 can divert a significant amount of Testosterone to aromatize into Estrogen that wouldn't have otherwise.
The consequence of this is a systemic elevation of Estrogen levels in the body, which is commonly misinterpreted as prohormone laced SARMs.
Common symptoms of high estrogen include:
- Acne, oily skin
- Erectile dysfunction
- Low libido
- Gynecomastia (man boobs)
- Water retention
- High blood pressure
- Enlarged prostate
- Shrunken testicles
- Sugar cravings
While LGD-4033 can cause Estrogen levels to rise via the increased aromatization of circulating Testosterone, long-term use, or high dosages of LGD-4033 can cause an opposite effect, where the body has such a low level of circulating Testosterone via endocrine suppression that the body no longer has enough aromatization occurring to satisfy Estrogen fulfilled physiological functions.
Low Estrogen levels can lead to a variety of health problems.
Common symptoms of low estrogen include:
- Dull weak orgasms
- Dry skin and lips
- Erectile dysfunction
- Low libido
- Mood swings
- Loss of appetite
- Decreased bone mass and strength
Applications In Alternative Hormone Replacement Therapy In Men
As Ligandrol does not aromatize into Estrogen, it would automatically be disqualified as a viable standalone hormone replacement therapy treatment for men.
Estrogen serves several important functions in the male body, and those functions rely on a sufficient amount of Estrogen being produced via the aromatization of endogenous Estrogen.
Low Estrogen side effects can be just as deleterious as high Estrogen side effects.
In a hypothetical scenario where Ligandrol would be considered as a potential long-term HRT treatment, it would very likely need to be used in conjunction with exogenous Estrogen to maintain healthy blood serum concentrations that would have otherwise been achieved via adequate Testosterone to Estrogen aromatization.
LGD-4033 exhibits a dose dependent increase in androgen activity in the body.
While it is extremely selective for muscle tissue and bone relative to androgen affected tissues, all SARMs (LGD-4033 included) result in systemic increases in androgen activity, therefore there will still be some potential for androgenic side effects.
The extent to which this will occur is just far less.
As LGD-4033 has an anabolic:androgenic ratio of greater than 500:1, the therapeutic dose necessary to yield the desired level of muscle and bone mineral density retention in hip fracture patients would very likely not be high enough where any notable androgenic activity could occur.
In a performance enhancement context, very high dosages would likely result in some notable androgenic side effects in the body.
All androgens can cause hair follicle miniaturization, the extent to which they do this is dependent on their individual selectivity, binding affinity, and the dosage used.
In general, therapeutic dosages of LGD-4033 should not cause any notable androgenic alopecia.
However, this does not exclude temporary shedding (acute telogen effluvium) which can be triggered by a hormonal fluctuation.
Any substantial shift in a man's hormone profile can cause hair roots to be pushed prematurely into the resting state.
Any hormonal fluctuation, stressor, autoimmune response, deficiency or chemical imbalance can potentially cause a temporary shed.
This is not to be confused with androgenic alopecia, which is permanent hair loss caused by androgen induced follicular miniaturization.
LGD-4033 did not result in any significant changes in AST or ALT levels in human trials [R].
However, it should be noted that in a relevant clinical trial conducted on Ostarine (a SARM with an identical mechanism of action), short-lived increases in ALT to above the upper limit of normal were observed in eight subjects [R].
Taking this into consideration, it's entirely possible that LGD-4033 could potentially also exhibit some degree of liver toxicity at dosages higher than the 1 mg trialed where they assessed those health markers.
At therapeutic dosages, there appears to be a strong safety profile and the data suggests a complete absence of liver toxicity.
Lack Of Aromatization And 5-Alpha Reduction
SARMs are resistant to metabolism by 5α-reductase and aromatase.
The most potent androgen in the prostate is dihydrotestosterone (DHT), which is formed by 5α-reduction of testosterone.
5α-reductase is expressed in high levels in the prostate, and very low levels in muscle tissue.
A study that assessed how much of a role endogenous DHT plays when it comes to building muscle discovered that it literally does nothing for gains in muscle mass, and that the conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle [R].
This is contrary to what many people assumed, as DHT on is such a potent androgen.
However, the fact that DHT is expressed in high levels in the prostate, but in low levels in muscle and bone, coupled with the data from that study, exhibits the true significance of DHT in prostate and testosterone in muscle and bone.
Ligandrol does not undergo 5α-reduction, which is speculated to contribute to its sparing effect on the prostate and other androgen affected tissues.
This is not the case though, as there are several androgens that do not undergo conversion to a more androgenic compound when undergo 5α-reduction.
One of the most notable being MENT (Trestolone).
Some androgens exhibit higher levels of androgenicity prior to 5α-reduction, and actually cause more androgenic side effects in the body when they are inhibited by 5α-reductase inhibitors.
A prime example of this is the anabolic androgenic steroid Nandrolone.
Ligandrol is inherently selective for the androgen receptor, and its selectivity for muscle tissue and bone relative to prostate is not a result of its inability to be altered by 5α-reductase.
LGD-4033 displayed a prolonged elimination half-life (24–36 hours), linear pharmacokinetics, and predictable accumulation with multiple dosing [R].
There was a dose-proportional increase in LGD-4033 concentrations on days 1 and 21 because of its long half-life.
Despite being reported to have a half-life of 24-36 hours, it would be wise for users to err on the side of caution and take into consideration that serum concentrations were nearly threefold higher on day 21 than on day 1 in the second Phase 1 trial.
This means that once daily dosing will result in concentration build up of the compound over time, as 24 hours is not enough clearance time to assume that once daily dosing will equate to stable blood serum concentration levels [R].
PCT (Post Cycle Therapy)
LGD-4033 will suppress natural Testosterone levels in a dose-dependent manner.
I believe it is essential to complete a PCT phase (post-cycle therapy) after a LGD-4033 cycle.
Due to the half-life of LGD-4033, PCT should be started the day after the last dosage was taken.
Forgoing PCT may greatly increase the risk of muscle loss, fat gain, among all of the other standard side effects associated with Testosterone suppression.
I would not advise following the standard “time on = time off” equation.
Disclaimer: The information included in this article is intended for entertainment and informational purposes only. It is not intended nor implied to be a substitute for professional medical advice.