A new blogpost about an old steroid, why? I was researching compounds that influence the libido, directly or with conjunction with other compounds. Than one of my clients told me he also used Proviron with Sustanon as HRT, especially because positively influenced his sex-life and worked well with the Sustanon. Discussing it with another friend that runs a gym and prepares men and woman for contests, he also told me he liked mesteronole (Proviron) very much and used it for diverse reasons but especially in contest preparation.
Mesterolone is one of the oldest anabolic steroids dating back to the 1930 years, along with methyl testosterone and testosterone propionate, even these steroids are still in use. The mesterolone applications are still not sufficiently well known, as is evident by several recent studies. In the beginning, these steroids were used to enhance the wellbeing of older men and also to improve mood and overall quality of life.
A group of Brazilian researchers, sometimes supplemented with American researchers, led by Karina Fontana, conduct a series of studies on effects of mesterolone in different groups of mice. These studies have been designed to procure more insights about the consequences of what they think, supra physiological doses of anabolic steroids in the form of mesterolone. Why mesterolone and not testosterone, the prototype of anabolic androgenic steroids? This has a number of reasons, * 1 oral bioavailability and * 2 no hepatoxicity * 3 no injection induced wound-formation or liver damage that would skew the results.
I know many readers hate scientific studies, especially if they are done on mice or rats. This group of researchers however, are using specially bred mice. The results are remarkable and often contradict the prevailing bro-science rhetoric that sounds so clear on the various discussion forums. Just take the time to read the abstracts and conclusions.
Adverse effect of the anabolic–androgenic steroid mesterolone on cardiac remodelling and lipoprotein profile is attenuated by aerobicz exercise training Karina Fontana, Helena Coutinho Franco Oliveira, Marta Beatriz Leonardo, Carlos Alberto Mandarim-de-Lacerda, and Maria Alice da Cruz-Höfling 2008:
“Abuse of anabolic–androgenic steroids (AAS) for improving physical performance is associated with serious, sometimes fatal, adverse effects. The aim of the present work was to investigate the effects of AAS on the cardiac structure and the plasma lipoprotein profile isolated and in combination with exercise.
Exercise training induced beneficial effects, such as physiological cardiomyocyte hypertrophy, increase in myocardial circulation and decrease in cardiac interstitium. However, mesterolone impaired such physiological gains and in addition increased troponin T plasma levels both in sedentary and exercised mice. Thus, while mesterolone induced pro-atherogenic lipoprotein profile and pathogenic cardiac hypertrophy, exercise counteracted these effects and modified favourably both the lipoprotein profile and the cardiac remodelling induced by mesterolone.”
Hepatocyte nuclear phenotype: the cross-talk between anabolic androgenic steroids and exercise in transgenic mice. Fontana K, Aldrovani M, de Paoli F, Oliveira HC, de Campos Vidal B, da Cruz-Höfling MA 2008
“The growing and indiscriminate use of high doses of anabolic androgenic steroid (AAS) among youth and athletes has raised serious concerns about its hepatotoxic effects. Herein, the influence of AAS in the nuclear phenotype of hepatocytes was investigated in sedentary and trained mice, heterozygous for the human. Five groups were assayed comprising treadmill exercised (Ex) and sedentary (Sed) mice, administered mesterolone (AAS) or gum arabic (GA) and a sedentary blank control. In this study, the image analysis permitted the monitoring of the nuclear response to mesterolone and physical exercise action in liver cells, the molecular mechanism of which is in prospect.
In conclusion, the present study is pioneering in demonstrating that the chronic use of mesterolone affects dynamically the status of chromatin condensation and texture, geometric parameters and Feulgen-DNA values in hepatocyte nuclei of sedentary and trained mice.
Mesterolone induced in sedentary mice the highest Feulgen-DNA content, which we credited both to the higher number of polyploidy cells and unpackaging of the chromatin associated to the highest increase of the nuclear size. The assessment of nuclear phenotype by image analysis can give clues to the mechanisms underlying the effects of AAS and its interplay with exercise effects in transcriptional activation or repression of eukaryotic genes. This study using a human-like lipemic mouse strain is part of a comprehensive study aimed to further understand the effects of AAS abuse.
We believe that this study will allow us to continue investigations to understand the mechanisms by which gene alterations and/or epigenetic factors provoked by the use of AAS may be linked with hepatocellular dysfunction.
In a recent study, we showed that the androgenic anabolic steroid mesterolone caused adverse cardiac remodeling and serious atherogenic lipoprotein profile in sedentary transgenic mice which express the human cholesteryl ester transfer protein (CETP) and are a
knockout for the low-density lipoprotein receptor (LDLr) (Fontana et al., 2008). In contrast, in mesterolone administered-treadmill exercised mice, the unfavorable cardiac remodeling and lipoprotein profile was markedly blunted.”
Effect of high intensity aerobic exercise and mesterolone on remodeling of Achilles tendon of C57BL/6 transgenic mice Fontana et all 2010:
Conclusion:“Thus, mechanical stimuli and mesterolone alter the morphology of tenocytes and the composition of the tendon, probably through fibrillogenesis and/or increased intermolecular cross-links. The ergogenic effect is evidenced by the activation of collagenous and non-collagenous protein synthesis and the increase in the diameter and area of collagen fibrils. This study might be relevant to clinical sports medicine.”
Morphological changes in murine skeletal muscle in response to exercise and mesterolone Fontana K, White KE, Campos GE, da Cruz-Höfling MA, Harris JB. 2010:
“Light and electron microscopy and quantitative morphometry were used to determine the effects of exercise and mesterolone on the soleus muscles of mice. Both exercise and mesterolone caused a significant hypertrophy of extrafusal muscle fibres. The hypertrophy of Type I fibres was greater than that of Type II fibres. There was no hyperplasia. Mitochondria were more numerous and larger than in the muscles of sedentary animals. Capillarity increased and small centrally nucleated muscle fibres appeared, usually in small clusters and most often in the muscles of animals exposed to mesterolone. A small proportion of satellite cells exhibited signs of activation but there were more in the muscles of mesterolone-treated animals than after exercise. Muscles from animals that had been both exercised and treated with mesterolone exhibited the largest changes: muscle mass and muscle fibre hypertrophy was greater than in all other groups of animals, capillarity was higher and >30% of all recognized satellite cells exhibited signs of activation.”
Groups of small centrally nucleated muscle fibres were commonly seen in these muscles. They appeared to be the result of splits in the form of sprouts from existing muscle fibres. With both exercise and mesterolone, alone or in combination, there was an increase in the proportion of Type I muscle fibres and a decrease in the proportion of Type II.”
Regulation of neuronal and endothelial nitric oxide synthase by anabolic-androgenic steroid in skeletal muscles K Fontana, T Rocha, MA da Cruz-Hoefling 2012
“Anabolic-androgenic steroids (AAS) and exercise share comparable effects on myogenic differentiation, force development, fiber growth and skeletal muscle plasticity. The participation of nitric oxide synthase (NOS) on these effects was only demonstrated in response to exercise. Using immunohistochemistry and western blotting we examined the effect of AAS on the expression of NOS I and III isoforms in three muscles.
Mice with a lipid profile akin to humans were used. Sedentary mice or exercised, submitted to six-weeks of aerobic treadmill running (one hour/day, 5 days/week) were administered mesterolone.
Mesterolone administered to sedentary mice significantly upregulated NOS I in TA and SOL and NOS III in all three muscles. Mesterolone administered to exercised mice upregulated NOS I in all three muscles and NOS III in TA and SOL. The exercise to mesterolone-treated mice produced a strong increase in NOS I expression.
These may be regarded as an indication of the complex NOS/NO signaling mechanism related with AAS effects vs. metabolic/physiological muscle characteristics.”
Effects of Anabolic Steroids and High-Intensity Aerobic Exercise on Skeletal Muscle of Transgenic Mice Fontana et all 2013
As such, three skeletalmuscles were studied under these experimental conditions: soleus (SOL), tibialis anterior (TA) and gastrocnemius (GA).
The animals either received gum arabic or the dihydrotestosterone derivative, mesterolone (M) (2 mg/kg body weight), during the last 3 weeks of the study (3d/wk: Monday, Wednesday, and Friday). The amount of mesterolone administered per week (6 mg/kg) is considered to be a high dose (supra-therapeutic) and is comparable to doses reportedly used in humans.
What the researchers believe to be supra-therapeutic (or unusual high dose) is in fact an unusual low dose. The rodents receive 3x2mg/kg Mesterolone per week on Monday, Wednesday and Friday. HUMAN EQUIVALENT DOSE (HED) = 2 mg/ kg for a mouse = 2 x [3 / 37] = 0.162 mg/kg, for a 100 kg athlete that is 16 mg. Bodybuilders and athletes normally use 50-150 mg/day.
Mesterolone (1 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) was chosen for three reasons: it can be administered orally avoiding injection induced wound formation and as a non-17 alpha-alkylated derivative of testosterone it presents low hepatotoxicity.
Overall, it is difficult to explain such varied findings concerning the effects of AAS treatment on fiber type distribution and size. Conflicting evidence may be due to a variety of factors: species, muscles chosen, androgen receptor density, fiber typing methodology, dosage/type of AAS, mode of administration, study duration, gender, age, and activity level.
Mesterolone and exercise each induced comparable increases in the size of all major fiber types in all three muscles. However, AAS plus exercise caused a cumulative effect resulting in additional hypertrophy.
These data were supported by similar increases in the muscle wet weights. The findings show that in this transgenic murine model the caloric expenditure induced by a metabolically-demanding exercise program was superimposed by protein synthesis resulting in muscle mass gains, which were potentiated in trained animals treated with mesterolone. Data obtained from this transgenic model (specifically engineered to express a lipemic phenotype akin to humans) could be relevant to humans from a comparative perspective.
How does mesterolone induce muscle growth?
Influence of mesterolone on satellite cell distribution and fiber morphology within maturing chicken pectoralis muscle Allouh et all 2012:
“Mesterolone is a synthetic oral anabolic androgenic steroid used to treat hypogonadism. There are frequent reports of mesterolone abuse in human and equine sports to increase muscle mass and strength. However, limited information is available about how this drug exerts its effects on skeletal muscle. Satellite cells (SCs) are mononuclear myogenic stem cells that contribute to postnatal muscle growth and repair. As SC activation and subsequent differentiation to new myonuclei is a major event during muscle hypertrophy.
This study indicates that mesterolone can induce avian skeletal muscle hypertrophy and that this is correlated with increased number of Satellite cells. We suggest that Satellite cells are key cellular intermediaries for mesterolone-induced muscle hypertrophy.”
Mesterolone treatment of aging male syndrome improves lower urinary tract symptoms Dugeroglu et all 2014
Their objective was to investigate the effects of mesterolone on prostate in patients treated for aging male syndrome. Their conclusion: “Mesterolone proved to be a safe alternative in the treatment of Aging Male Syndrome. It also improved lower urinary tract symptoms and prostate-related quality of life.”
Newer research indeed suggests mesterolone to improve mood.
From the same study: “Nowadays it is well known that one of the main physiological functions of testosterone is to tune up erection with sexual desire, finalizing erection to emotional processing. Testosterone replacement therapy (TRT) has been described to significantly improve cognitive function in the general population, and also in the depressed men. More recently, also the negative symptoms in male schizophrenic patients have been correlated with serum testosterone level and short-term testosterone treatment has been suggested as a therapeutic option in male schizophrenics. “
Most guys hate to excerpts from scientific studies, but I’ll think you need to see this one:
“Forty subfertile men with idiopathic oligospermia were randomly treated with mesterolone or with placebo for more than 4 months. Seminal analysis was performed thrice before treatment, and twice after 16 weeks of treatment. There was a significant increase of semen volume, mean sperm concentration, and mean total sperm count per ejaculate (P less than .01) with mesterolone therapy.”
Mesterolone for Women
Long-term treatment of renal anaemia with mesterolone. Kraft D 1980:
Which made a girl rave on a discussion forum: “Hirsutism is NOT wanted, but this was a dose of 150mg, whereas 10-25mg will be enough to get the libido racing ”
A nice set of studies on axis suppression I found on the net:
This thread is regarding Proviron used standalone for non-cycle, non-PCT purposes such as strength gain or aggression in the weight room, libido, muscle hardening, etc. I’ve often wondered if suppression would become a significant issue when it’s used for sometimes prolonged periods in someone with a normal hormonal environment, and if PCT is necessary when using it like this. I’ve complied a group of studies to find out.
#1 : The effect of mesterolone on sperm count, on serum follicle stimulating hormone, luteinizing hormone, plasma testosterone and outcome in idiopathic oligospermic men.
Two hundred fifty subfertile men with idiopathic oligospermia (count less than 20 million/ml) were treated with mesterolone (100-150 mg/day) for 12 months. Seminal analysis were assayed 3 times and serum follicle stimulating hormone (FSH) luteinizing hormone (LH) and plasma testosterone were assayed once before treatment and repeated at 3, 6, 9 and 12 months after the initiation of treatment. One hundred ten patients (44%) had normal serum FSH, LH and plasma testosterone, 85 patients (34%) had low serum FSH, LH and low plasma testosterone.
NOTES: Used a large group, most of whom were hormonally normal. LH lowered a bit if it was elevated, but not really relevant because testosterone levels showed no significant change in all subjects anyways.
#2 :Mesterolone treatment of patients with pathospermia.
The response to Mesterolone, in doses of 25 mg/day, was examined in 42 pathospermic patients. Treatment lasted for 100 days. The pronounced response to the Mesterolone treatment was observed in hypozoo- and oligozoospermia with low initial fructose content in the ejaculate. Fructose content attained its normal range after the treatment. During the therapeutic period 11 wives became pregnant. The authors conclude that Mesterolone does not influence plasma FSH, LH and testosterone levels, it has only peripheral effects.
NOTES: Low dose over a decent 3 month time frame. No measurable influence on HPTA.
#3 : Plasma cholesterol, triglycerides, FSH and testosterone levels of normolipemic male patients with decreased fertility treated with mesterolone.
There were no changes in plasma cholesterol, triglycerides, FSH and testosterone levels of 24 healthy men treated with mesterolone for infertility during period of 6 months. The patients were normolipemic and the daily doses were 75 mg. No side-effects were noticed. Mesterolone seems to have too selective or too low androgenic effect with the doses used in orde to have an influence on the lipid metabolism of men.
NOTES: Decent sized group, again healthy, apart from being infertile. Low-medium dose for a pretty long time period. Again no significant suppression.
# 4: The effects of mesterolone on the male accessory sex organs, on spermiogram, plasma testosterone and FSH.
42 subfertile male ambulatory patients were treated with Proviron. Moderate oligoastheno-teratozoospermia was the most common injury in sperm analysis. The treatment did not change the amount of plasma FSH, testosterone or prostate phosphatase. Acid phosphatase and citric acid of semen showed an increased activity with mesterolone treatment. The amount of fructose decreased, it is probably due to the increased number of spermatozoa, which need more fructose for their metabolism respectively. The sperm of 93% of the patients improved or stayed unchanged. 30% of the patients developed normozoospermia. 6 pregnancies were achieved.
NOTES: Here, as well as being infertile, the patients are also bedridden. The reasons for this are not given. Nor is the daily dose amount of mesterolone. By itself, this study is hardly anything at all, but taken together with the above studies which also failed to detect endocrine changes, it can be suggestive and so should be considered.
#5 : Effect of non aromatizable androgens on LHRH and TRH responses in primary testicular failure.
We have assessed the gonadotropin, TSH and PRL responses to the non aromatizable androgens, mesterolone and fluoxymestrone, in 27 patients with primary testicular failure. All patients were given a bolus of LHRH (100 micrograms) and TRH (200 micrograms) at zero time. Nine subjects received a further bolus of TRH at 30 mins. The latter were then given mesterolone 150 mg daily for 6 weeks. The remaining subjects received fluoxymesterone 5 mg daily for 4 weeks and 10 mg daily for 2 weeks. On the last day of the androgen administration, the subjects were re-challenged with LHRH and TRH according to the identical protocol. When compared to controls, the patients had normal circulating levels of testosterone, estradiol, PRL and thyroid hormones. However, basal LH, FSH and TSH levels, as well as gonadotropin responses to LHRH and TSH and PRL responses to TRH, were increased. Mesterolone administration produced no changes in steroids, thyroid hormones, gonadotropins nor PRL. There was, however, a reduction in the integrated and incremental TSH secretion after TRH. Fluoxymesterone administration was accompanied by a reduction in thyroid binding globulin (with associated decreases in T3 and increases in T3 resin uptake). The free T4 index was unaltered, which implies that thyroid function was unchanged. In addition, during fluoxymesterone administration, there was a reduction in testosterone, gonadotropins and LH response to LHRH. Basal TSH did not vary, but there was a reduction in the peak and integrated TSH response to TRH. PRL levels were unaltered during fluoxymesterone treatment.
NOTES: This one is a bit different, as they also gave injections of LHRH. In this small group of subjects, Proviron didn’t measurably change the response of LH and FSH (and ultimately testosterone) to LHRH after it had been taken at a medium dose for several weeks. Good to know.
The following DO show suppression with Proviron use:
#6 : The effects of mesterolone, a male sex hormone in depressed patients (a double blind controlled study).
Based on computer EEG (CEEG) profiles, in high doses, antidepressant properties of mesterolone, a synthetic androgen, were predicted. In a double-blind placebo controlled study, the clinical effects of 300-450 mg daily mesterolone were investigated in 52 relatively young (age range 26-53 years, mean 42.7 years) male depressed outpatients. During 6 weeks of mesterolone treatment, there was a significant improvement of depressive symptomatology. However, since an improvement was also established during the placebo treatment, no statistically appreciable difference in the therapeutic effects of mesterolone was established compared to placebo. Mesterolone treatment significantly decreased both plasma testosterone and protein bound testosterone levels. Patients with high testosterone levels prior to treatment seem to have had more benefit from mesterolone treatment than patients with low testosterone levels. The degree of improvement weakly correlated to the decrease of testosterone levels during mesterolone treatment.
NOTES: A decent sized group of middleaged men given 300-450 mg for several weeks. That’s at least 2-3X the dose given in the studies above.
#7: The hormone response to a synthetic androgen (mesterolone) in oligospermia.
Forty subfertile men with oligospermia were treated with a synthetic androgen (Mesterolone). The effect of the drug was evaluated by measuring serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and analysing the semen before and after treatment. The results demonstrated that in twenty-three patients treated for 6-9 months there was a significant decrease in serum testosterone (P less than 0.01); the means +/- SEM before and after treatment were 17.05 +/- 0.95 and 14.7 +/- 0.95 (nmol/l serum) respectively. There was a pronounced increase in serum LH (P less than 0.01), the values being 2.73 +/- 0.26 and 3.61 +/- 0.3 (u/l) respectively. However, no significant difference was found in serum FSH before and after treatment. The sperm concentration showed a variable response to treatment. In twenty-one patients there was either no change or worsening in the sperm concentration, whereas in nineteen patients an improvement was observed. The analysis of variance of sperm concentration and motility for the periods before and after treatment, for all the patients, showed no significant difference in the sperm concentration F1.145 = 2.82 (P=0.1).
NOTES: This group was treated for a long time, with testosterone decreasing, but again the dosage used is unknown. Considering the above, it’s safe to assume they used high doses, like in #6. Strangely, LH is increased, but this may be due to its pulsatile nature, which makes it more difficult to measure precisely.
CONCLUSION: Just looking at all the subjects in studies 1-4 you see a total of 358 ppl with normally functioning endorine systems take anywhere from 25-150 mg, sometimes for up to 12 months or more, with no measurable change in testosterone. Studies which showed otherwise used or were likely to have used very high doses. Low to medium doses (25-150 mg) of proviron taken when you’re HPTA is fully functioning (read: not at the end of a cycle) does not significantly suppress testosterone. Higher doses however have a tendency to.
This is what you normally find on the net about Proviron (mesterolone):
Mesterolone has four distinct uses in the world of bodybuilding. The first being the result of its structure. It is 5-alpha reduced and not capable of forming estrogen, yet it nonetheless has a much higher affinity for the aromatase enzyme (which converts testosterone to estrogen) than testosterone does. That means in administering it with testosterone or another aromatizable compound, it prevents estrogen build-up because it binds to the aromatase enzyme very strongly, thereby preventing these steroids from interacting with it and forming estrogen. So Mesterolone use has the extreme benefit of reducing estrogenic side-effects and water retention noted with other steroids, and as such still help to provide mostly lean gains. It’s also been suggested that it may actually downgrade the actual estrogen receptor making it doubly effective at reducing circulating estrogen levels.
The second use is in enhancing the potency of testosterone. Testosterone in the body at normal physiological levels is mostly inactive. As much as 97 or 98 percent of testosterone in that amount is bound to sex hormone binding globulin (SHBG) and albumin, two proteins. In such a form testosterone is mostly inactive. But as with the aromatase enzyme, DHT has a higher affinity for these proteins than testosterone does, so when administered simultaneously the mesterolone will attach to the SHBG and albumin, leaving larger amounts of free testosterone to mediate anabolic activities such as proteinsynthesis. Another way in which it helps to increase gains. It’s also another part of the equation that makes it ineffective on its own, as binding to these proteins too, would render it a non-issue at the androgen receptor.
Thirdly, mesterolone is added in pre-contest phases to increase a distinct hardness and muscle density. Probably due to its reduction in circulating estrogen, perhaps due to the downregulating of the estrogen receptor in muscle tissue, it decreases the total water build-up of the body giving its user a much leaner look, and a visual effect of possessing “harder” muscles with more cuts and striations. Proviron is often used as a last-minute secret by a lot of bodybuilders and both actors and models have used it time and again to deliver top shape day in day out, when needed. Like the other methylated DHT compound, drostanolone, mesterolone is particularly potent in achieving this feat.
Lastly Proviron is used during a cycle of certain hormones such as nandrolone, with a distinct lack of androgenic nature, or perhaps 5-alpha reduced hormones that don’t have the same affinities as DHT does. Such compounds, thinking of trenbolone, nandrolone and such in particular, have been known to decrease libido. Limiting the athlete to perform sexually being the logical result. DHT plays a key role in this process and is therefore administered in conjunction with such steroids to ease or relieve this annoying side-effect. Proviron is also commonly prescribed by doctors to people with low levels of testosterone, or patients with chronic impotence. It’s not perceived as a powerful anabolic, but it gets the job done equally well if not better than other anabolic steroids making it a favorite in medical practices due to its lower chance of abuse.