LGD-4033 (Ligandrol) -Recreational Use, Clinical Trials & Reviews

ABSTRACT: Selective androgen receptor modulators (SARMs) are anabolic compounds that bind to androgen receptors. They have been studied as potential treatments for cancer, osteoporosis, sexual dysfunction, multiple sclerosis, Alzheimer’s disease, and muscle wasting. Recently, SARMs have been placed in various supplements marketed to fitness enthusiasts. SARMs have been found to reduce endogenous testosterone, affect cholesterol levels, and alter liver function. Recreational users of SARMs may take them in combination with each other on a cyclical basis. They may also practice postcycle therapy, which involves the use of SERMs in between cycles to help restore hormone balance.

LGD-4033 is one of the strongest in its class selective androgen receptor modulator (SARM). As a matter of fact, it is one of the newest SARMs that have come out, and is the closest SARM that can be equated to an anabolic steroid when it comes to pure strength. Hence, it is the strongest SARM mg for mg in terms of the mass you can put on.

LGD-4033 is an investigational selective androgen receptor modulator (SARM) for treatment of conditions such as muscle wasting and osteoporosis, discovered by Ligand Pharmaceuticals and currently under development by Viking Therapeutics.

LGD-4033 is currently an Investigational New Drug.

LGD-4033 is commonly incorrectly referred to as “Anabolicum”, which is actually the brand name for the anabolic androgenic steroid Quinbolone developed by Parke-Davis [R, R].

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.

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].

Several clinical trials using transdermal testosterone for female sexual dysfunction in women with low serum testosterone showed improvements in sexual desire, pleasure, and orgasms.

Given the evidence surrounding the utility of androgens in treating postmenopausal genitourinary symptoms and inhibited sexual desire in women, SARMs represent a potentially attractive future therapy.

In men, there is little controversy surrounding the critical role of testosterone in male libido and sexual function. Many trials and studies have established the sexual benefits of exogenous testosterone use for men. For example, in a cohort of hypogonadal men treated chronically with testosterone gel, scores quantifying sexual desire, enjoyment, erection quality, and sexual activity were all markedly and sustainably improved from baseline. Similar to the preclinical data discussed previously in regard to SARMs and female sexual function, treatment of male rats with SARMs led to increased sexual behavior. These results suggest that SARMs could be as effective as treatment with testosterone and its derivatives in promoting male libido.

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].

LGD-4033 works by binding to androgen receptors selectively, meaning that it creates anabolic activity only in bones and muscles, instead of harming prostate and sebaceous glands, like anabolic steroids do. In fact, volunteer human studies have shown that LGD 4033 was harmless when used with a dose under 22 milligrams (mg) per day. Furthermore, studies also showed that LGD enhances lean muscle mass and decreases body fat; all of which comes with an incredible ability to boost strength, recovery and overall health.

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].

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.

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.

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.

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.

As mentioned above, LGD4033 is the most potent SARM in its class and the closest one to anabolic steroids. However, it comes without the harsh side effects and severe suppression of anabolic androgenic steroids (AAS). Therefore, athletes who compete in strength sports (American football, field sports, rugby, hockey, and weightlifting) will appreciate LGD the most.

What’s more, powerlifters love LGD because of its rapid strength improvements – typically, when dosing at only 10mg per day for under 8 weeks they will see noticeable improvements to their lifts across the board.

Interestingly, although not known for its healing properties, LGD does not tear up the soft tissues like anabolic steroids, but rather keeps them strong because of its ability to bind to receptors in bones. Thus, just like with all SARMs, there is plenty of versatility with LGD, which can be run solo, or stacked with other SARMS and/or anabolic steroids. As a result, the athlete has many different options depending on their goals.

Despite the growing use and purported safety of SARMs in the fitness and bodybuilding communities, very few clinical studies aimed at understanding their pharmacokinetic profiles and identifying potential adverse effects and drug interactions have been performed.⁷ Consequently, their long-term effects on the body remain largely unknown. Clinical experience with SARMs is largely from illicit use rather than clinical studies.⁷ Additionally, in the fitness community, SARMs are taken at doses and durations that are higher than those tested clinically. The interactions of SARMs with other substances (e.g., alcohol and other drugs) with chronic use, particularly at high doses, remains unknown.

Developed by Ligand Pharmaceuticals, there has been only one clinical trial involving the drug.²⁰ In the placebo-controlled study, 76 healthy men were randomized to placebo or 0.1 mg, 0.3 mg, or 1.0 mg LGD-4033 daily for 3 weeks. The drug was well tolerated, with no serious adverse drug-related events. Hemoglobin, prostate-specific antigen, aspartate aminotransferase (AST), ALT, and QT intervals were not altered at any dose. At the 1.0 mg dose, follicle-stimulating hormone and free testosterone were significantly suppressed; there was no change in luteinizing hormone. Hormone levels returned to normal when the treatment was discontinued. Lean body mass increased dose-dependently, but there were no statistically significant changes in fat or appendicular skeletal muscle mass. Strength and stair-climbing speed and power trended toward a dose-dependent improvement but were not statistically significant. Total and low density lipoprotein (LDL) cholesterol did not change significantly from baseline at any dose. Although HDL increased at the 0.3 and 1.0 mg doses, it returned to normal upon discontinuation. Triglyceride levels decreased from baseline at all doses. Headache and dry mouth were the most common side effects. In a recent case report, a healthy 24-year-old man displayed signs of hepatocellular liver injury.²¹ These symptoms developed a week after drug cessation. The man had a history of binge drinking, was not on regular medications, and had no previous history of liver disease. Of concern, this hepatotoxicity lies within the spectrum of liver injury associated with androgenic anabolic steroids.

There are a ton of different reasons to use ligandrol over some of the other options out there. Here are just a few of the benefits of LGD 4033:

Increase Muscle Mass

The most obvious benefit of taking ligandrol is how quickly it can promote a gain of muscle mass (source). It is not uncommon for an athlete to gain 10lbs of pure muscle in a typical 8 week cycle. Many people compare this SARM to steroids like Dianabol for this reason.

Reduction of Fat

Although ligandrol does not directly burn fat, it will definitely help retain muscle on a cut. Studies also show that people with more muscle mass will naturally stay more lean than people with very little muscle. It’s safe to say that using this SARM to lean up can be a very effective way to produce results on a cut. If you are looking for a more reliable way to lose fat with sarms, you might want to consider ostarine and/or cardarine.

Alpha Feeling

One of the effects of using SARMs are the ability to promote an “alpha” or more manly feeling for those using them. This is especially true with LGD 4033. In fact, this user on reddit claims that he felt more “energized, motivated, and confident” at work! This is a huge benefit for a lot of people who want to increase the way they feel on top of the way that they look.

Huge Strength Gains

One of the great things about LGD-4033 is it’s ability to rapidly provide strength gains for users. For this reason, it is a very popular drug in powerlifting circles. This user on the AnabolicMinds forum posted his strength increases after a cycle of LGD. It’s pretty amazing how fast he gained strength. In one month, here are his strength increases:

• 12lbs increase in body weight
• 60lbs increase in squat
• 45lbs increase in bench press
• 60lbs increase in deadlift
• 35lbs increase in standing press

All done in just one month! We’ve been studying performance enhancing drugs for a long time, and those numbers are the types of things you see with hardcore steroids. The fact that they were achieved with no side effects is pretty remarkable.

Side Effects Of Ligandrol

LGD 4033 is generally regarded to be a very safe compound when used appropriately. In fact, this study done in 2012 said the following about side effects:

 LGD-4033 was well tolerated. There were no drug-related serious adverse events. Frequency of adverse events was similar between active and placebo groups.

This is a big deal for a few reasons.

First of all, it says that side effects experienced were no different between those who took ligandrol the placebo group. In a nutshell, this study shows that you can experience the benefits of steroids without any of the side effects. All of the people in the study showed an increase of LBM (lean body mass).

That study was seven years ago, and thousands of people have used LGD 4033 since then. With that being said, there are bound to be some users who report side effects. They are extremely rare, but they can happen. Let’s take a look at some of them.

Hair Loss from LGD 4033

Most people agree that ligandrol is at least slightly androgenic. People who are already balding severely or are predisposed to balding might experience more shedding than normal. This report on reddit shows a user asking if they are being paranoid, or if LGD can actually cause hair loss. The general consensus seems to be that he was being paranoid, and that LGD 4033 does not cause hair loss.

Testosterone Suppression

Suppression of testosterone is bound to happen when taking most SARMs, and that’s okay. In fact, it is expected. When taking an external hormone, whether it is a SARM, steroid, or prohormone, your body will temporarily stop producing it’s full supply of testosterone.

The good news is that your body bounces back very quickly on SARMs vs testosterone or prohormones. In fact, you will only be suppressed while on cycle, and your body will usually be in full swing 30 days after you stop taking sarms. With steroids it can take 9 months to a year, and some people never recover. Keep your cycle of LGD to 8 weeks or shorter and you will not run into any issues.

High Blood Pressure

This is another one of those inevitable side effects that is so mild that most people don’t notice. LGD 4033 will cause an elevated blood pressure level while on cycle. It is important to note, however, that this is a temporary side effect that will correct itself once you stop taking it. It is not a dangerous side effect, and in fact it is a sign that the source you are using is legit.

You can expect to gain quite a few pounds of lean body mass (muscle) during your ligandrol cycle. With that being said, your results of taking LGD 4033 will vary depending on quite a few factors. Some of these include:

• What type of diet you follow and your protein intake.
• Training routine, volume, and intensity.
• Your dosage and cycle length.

Let’s break it down and give you some more accurate ideas of what to expect from your cycle.

Bulking Cycle Results

If you are bulking, you can expect to gain 10 to 15lbs over an eight week cycle. This is assuming proper dosage (see below) and adequate protein and carb intake. It is important to get at least one gram of protein per pound of bodyweight per day. For example, if you weigh 210lbs, you should aim to get 210g of protein per day while on cycle.

For bulking cycles, you should also be doing lots of compound exercises in your training routine. Work big muscle groups and focus on adding weight to the bar. Do not be afraid of carbs, either. A good post workout meal will include 50-75g of protein and 150g+ of carbs. The lgd-4033 will help push those carbs directly into your muscle.

Cutting Cycle Results

We don’t usually recommend LGD 4033 for a cut, however we know that others do. With that being said, you can expect to put on a few (think 3 to 5) pounds of muscle while losing fat. How much fat you lose will be entirely dependent on your diet, since LGD 4033 does not directly burn fat or encourage fat oxidation.

We would recommend a low carb diet, combined with daily fasted cardio and a full body workout routine done three times a week to prevent muscle decay.

If we had a say in it, we would recommend an ostarine and cardarine stack for cutting. We will have a guide up on that stack soon enough.

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.

LGD-4033 Dosage

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.

Side Effects

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.

Testosterone Suppression

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
• Lethargy
• Gynecomastia (man boobs)
• Irritability
• Depression
• 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
• Dehydration
• Erectile dysfunction
• Low libido
• Irritability
• Mood swings
• Loss of appetite
• Fatigue
• Lethargy
• 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.

Androgenic Activity

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.

Hair Loss

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.

Liver Toxicity

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.

Half-Life

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].

LGD-4033 Bulking Cycle

In a calorie surplus LGD-4033 will promote more lean muscle gains than would otherwise be possible to gain naturally.

For use in a performance enhancing context, cycles like the following are commonplace among users.

MK-677 (Ibutamoren) and SARMs like RAD140 or S4 are commonly stacked alongside LGD-4033 in more involving performance enhancement bulking protocols.

LGD-4033 Cutting Cycle

In a calorie deficit LGD-4033 will retain much more lean muscle mass than would otherwise be possible naturally.

For use in a performance enhancing context, cycles like the following are commonplace among users (the length of this may vary depending on the user’s individual timeline constraints for reaching a goal body fat percentage).

Cardarine (GW501516) and SARMs like RAD140 or S4 are commonly stacked alongside LGD-4033 in more involving performance enhancement cutting protocols.

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 will greatly increase the risk of muscle loss, fat gain, among all of the other standard side effects associated with Testosterone suppression.

How much time off you should take after your PCT should be dictated by a variety of individual specific factors and blood work.

I would not advise following the standard “time on = time off” equation.