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There were 135 PubMed-indexed Studies about SARMs (steroid androgen receptor modulators) at the end of January 2019.

SARMs were a hot topic in American Society of Bone and Mineral Research conference held in Quebec, Canada. The established technologies for improvement of bone function are high dose vitamin D, bisphosphonate drugs and somewhat more novel combination therapy of monoclonal antibodies that attack osteoclasts.  They are cells that normally remodel the bone but cause osteoporosis if their proportion is out of balance. And recombinant parathyroid hormone that supports osteoblasts (bone-building cells) if used intermittently [1]. However, the SARMs were the most interesting from the novelty perspective.

SARMS overview 2019

A really interesting study published in 2019 discusses a SARM found from the nature (wild bitter gourd extract). It compared the SARM with testosterone in castrated mice (to unmask the effects of treatment from endogenous male steroid hormones). While testosterone increased the mass of both muscles and male accessory glands (prostate and seminal vesicles), the bitter gourd extract increased grip strength and acrobatic/balance performance measured with as measured by the typical rotarod test [2]. Boosting mitochondria and their oxidative capacity as well as negating castration-induced muscle decline was proposed as mechanism of action.

A review paper was also published in 2019. It is somewhat a non-news that no SARMs are available as prescription drugs. In summary, the research has found that these molecules seem to have few if any drug interactions and the clinical studies suggest potential future applications for pathological muscle loss, benign prostate hyperplasia (BPH), hypogonadism and breast cancer [3]. As well as, possibly, Duchenne muscular dystrophy (a disease which causes progressive weakness of muscles that is eventually lethal due to withering of breathing muscles). In contrast to uses related to disease, the use of SARMs as performance-enhancing agents was briefly discussed, as these drugs have anabolic effects with less side effects (without excluding potential for abuse). That make SARMs interesting for bodybuilding community.

SARMS overview 2018

In addition to regular additions to the set of studies dedicated to development of methods of doping detection. Few other studies were published in 2018. Like “development of transdermal system of administration of SARM LY305” [4]. It improved the speed of muscle and bone repair without overt adverse effects in laboratory rodents, and was well-tolerated in human volunteers. Another study discovered that SARM S42 inhibited proliferation of prostate cancer cell line PC-3 [5]. Third study, expectedly, found that YK11 supported the function and proliferation of bone-building osteoblast cells of mice [6]. Another study weighed in additional evidence by showing the anti-osteoporosis effects for the currently perhaps the best-known SARM ostarine [7].

Animal studies (especially optimistic ones for the sake of caution) must be taken with a grain of salt, though. A study found that LGD-4033 (that may also be known as ligandrol) metabolizes moderately differently in humans and horses. Which adds a layer of complexity to interpretation of animal studies in general as well as doping detection in different species specifically [8].

While the aim of this text was to summarize the studies published in 2019 and 2018, a few studies of interest were published in 2017 deserve mentioning. We will cover this in future posts.

[1] https://www.ncbi.nlm.nih.gov/pubmed/30590370
[2] https://www.ncbi.nlm.nih.gov/pubmed/30600821
[3] https://www.ncbi.nlm.nih.gov/pubmed/30503797
[4] https://www.ncbi.nlm.nih.gov/pubmed/29527831
[5] https://www.ncbi.nlm.nih.gov/pubmed/29444261
[6] https://www.ncbi.nlm.nih.gov/pubmed/29491216
[7] https://www.ncbi.nlm.nih.gov/pubmed/29785666
[8] https://www.ncbi.nlm.nih.gov/pubmed/29334634

There’s a new review paper on an interesting topic, titled “Novel Therapy for Male Hypogonadism” from Miami University. We are let known that the last author of the paper [1] was the lead investigator of a drug trial in the past (Natesto, a formulation of testosterone for hypogonadism). The researchers are from Miami. Whether its tropical climate and beautiful beaches play a role on choice of the topic, remains unknown.

Low testosterone

Word ‘hypogonadism’ comes from Ancient Greek – hypo meaning sub-; gonad meaning seed). Hypogonadism is a clinical entity diagnosed with repeated measurement of low testosterone. Clinically, age-related hypogonadism is a type of sexual development delay in boys. Late-onset of hypogonadism can resemble some aspects of old age that are not liked very much by older men.

The paper discusses the recent papers on the clinical meaning of hypogonadism. One of the key issues is that older men with the hypogonadism complaints do not have low testosterone and vice versa.

Several treatment options are available. In addition to physical activity and lifestyle modification that is very important for late-onset hypogonadism. Testosterone replacement treatment is the approved treatment while several experimental treatment options have been used as off-label treatments or in scientific studies.

Testosterone replacement is effective against hypogonadism symptoms. But is likely to adversely affect endogenous testosterone production and fertility parameters.

Selective estrogen receptor modulators (SERMs)

Selective estrogen receptor modulators (SERMs) have different estrogenic and antiestrogenic activity. SERMs such as tamoxifen and clomiphene improve serum lipids and bone density but tend to increase the incidence of venous thrombembolia. A SERM, Clomiphene citrate works by reducing negative feedback from estradiol to hypothalamus. That is at the top of cascade leading to testosterone production. Clomiphene is quite widely used by doctors despite indication being off-label. Clomiphene raises rather than suppresses endogenous testosterone, and spares fertility, and the cost to the patient is lower.

Aromatase inhibitors such as anastrozole and exemestane work by reducing conversion of testosterone to estradiol. Estradiol in low doses has beneficial effects but increased levels of estradiol cause undesirable effects other than negative feedback to hypothalamus as well. That can be summarized as feminization. While clomiphene is better at increasing testosterone concentration, aromatase inhibitor anastrozole was better at increasing testosterone : estradiol ratio.

Human chorionic gonadotropin (HCG) can raise endogenous testosterone production but also FSH is necessary for preservation of fertility. HCG has been used to treat azoospermia caused by steroid abuse. It may be combined with testosterone replacement to preserve the intratesticular levels of endogenous testosterone and and normal semen parameters.

Anabolic steroids such as nandrolone have also been revisited, lately, and considered as possibilities alternative to testosterone replacement because anabolic steroids have desirable effect of muscle selectivity

SARMs

Finally, SARMs are considered as a novel option for testosterone replacement treatment. The selectivity of SARMs is more desirable than that of anabolic steroids, largely lacking androgenic activity in prostate or sebaceous glands, therefore making these compounds interesting for future pharmacy. However, as is often the case with novel substances – more research is needed before more widespread application may take place.

Source:
https://www.ncbi.nlm.nih.gov/pubmed/29886559

One may only wonder, which of the above would be the first to be considered as an alternative to testosterone replacement treatment first.

We have added YK11 overview. YK11 is not much researched SARM, but it has interesting and different mechanism of action than other SARMs.