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marylin monroe
Showing posts with label aromatase inhibitor. Show all posts
Showing posts with label aromatase inhibitor. Show all posts

TReaTing Diabesity With Testosterone!? If You Keep DHT in Check + Stay Away From Aromatase Inhibitors, It May Work

It probably won't turn an overweight pre-diabetic into a fitness model, but a getting a TRT script has the potential of changing a man's physical and psychological health for the better.
Despite the fact that more and more men recognize the benefits of supervised testosterone replacement therapy (TRT) and the bodybuilding and fitness community cherishes 'their BIG T' as the be-all-and-end-all, many medical practitioners look at the administration of exogenous androgens as a potential health hazard. I would even bet that it won't be difficult to find one or two MDs who would say that Patricia S. Juang et al.'s idea to administer testosterone to obese men with normal, but low baseline testosterone levels to improve their body composition and insulin sensitivity borders physical injury - and that irrespective of adjuvant 5α-reductase (dutasteride) or aromatase (anastrazole) inhibitor administration.

TRT w/ or w/out aromatase or 5α-reductase inhibitor?

It goes without saying that the bodybuilding enthusiasts will think very differently about the usefulness of the 10 g testosterone gel (Testim) the fifty-seven 24–51-year old men with free testosterone levels in the lower 25% of normal range (<0.33 nmol/L) and a body mass index of ≥30.0 kg/m² in this recent  98-day randomized, double-blind, parallel group, placebo-controlled trial from the Universities of California and the Boston University Medical Center (Juang. 2013). In fact, I am pretty sure that, contrary to the scientists who put their subjects on either
  • + subjects received a gonadotropin releasing-hormone antagonist to suppress endogenous T production
    10g Testim per day,
  • 10g Testim + 1mg Arimidex (anastrazole) per day, or
  • 10g Testim + 2.5 mg Avodart (dustasteride),
some of the physical culturists may even have suggested to use both, the aromatase inhibitor Arimidex and the 5α-reductase inhibitor Avodart to make absolutely sure that the T remains T and is not converted to estrogen or DHT.
Figure 1: Change in hormone levels (left) and body composition (right) after 98 days on 10g t-gel (Testim) with / without aromatase (Arimidex) or 5α-reductase (Avodart) inhibitor (Juang. 2013)
If they looked at the data in Figure 1, the estrogen-phobic bodybuilding enthusiasts would yet have to admit that the "bad estrogen" cannot be so bad as broscience would have it. Only minimal decreases in body fat, and significantly lower increases in fat free mass in the presence of a 5cm! (+4%) increase in waist circumference is certainly not what the bros are looking for.
Looking for natural ways to boost your testosterone levels? Look no further! You can learn about 10 ways to up your testosterone levels in my previous article "Natural Hormone Optimization Made Simple & Cheap: Avoid These 10 Anti-Androgens to Boost Testosterone & DHT" | read more
As surprising as the magnitude of the 'waist gain' may be, I personally have been more surprised by the effects the 10g of Testim had on the DHT levels of the overweight subjects. In both, the T-only and the T + Arimidex group the DHT level literally exploded and blunted the 25%, respectively 30% increase in glucose disposal during  minutes 120–180 and 240–300 of the euglycemic hyperinsulinemic glucose clamp test the scientists performed before and after the intervention period (Juang. 2013).

Despite a -40% decrease in PSA (vs. +9% in the T-only group), the 5α-reductase inhibitor dustasteride did not prevent the ~10% increase in prostate size that occurred in both the T-only (12%; +9% PSA) and T + Acodart (10%; -40% PSA) group. Other safety markers, such as AST (liver) or haemoglbin (iron overload) did not change.
The fact that dustasteride does not blunt testosterone induced lean mass gains is something you may have read in a previous article | more
Bottom line: I guess there are three things we can take away from this study:
  1. TRT can help overweight men with impaired insulin resistance improve their body composition.
  2. The administration of an aromatase inhibitor blunts the beneficial effects and causes a surprisingly pronounced increase in waist circumference.
  3. The glucose sensitivity increases only, when the excessive reduction of testosterone to DHT is blocked by dustasteride.
In other words, if you want the T accept the E, but watch your DHT; but remember: Don't do it without blood work!
References:
  • Juang, P. S., Peng, S., Allehmazedeh, K., Shah, A., Coviello, A. D. and Herbst, K. L. (2013), Testosterone with Dutasteride, but Not Anastrazole, Improves Insulin Sensitivity in Young Obese Men: A Randomized Controlled Trial. Journal of Sexual Medicine.

T-Gel with or Without an Aromatase Inhibitor? If You Are Healthy & Lean and Want to Stay This Way, There is Only One Answer: T-Gel Without Aromatase Inhibitor!

Don't let her talk you into participating in studies that risk your manliness ;-)
Would you be willing to participate in a study, where you could end up without testosterone? No? Well me neither... strangely Joel S. Finkelstein et al. were able to find 198 healthy men between 20 and 50 years who were stupid enough to participate in an experiment, where they were randomized to placebo, or testosterone gel (1.25, 2.5, 5, or 10g per day) while being on gosererelin acetate, which did suppress their natural testosterone production.

With additional 202 subjects receiving an identical "treatment", but in this case alongside a whoppy dose of the aromatase inhibitor anastrazol as a bonus, the study design leaves us with plenty of groups and tons of subjects. To "determine the relative degree of testosterone deficiency, estradiol defi­ciency, or both at which undesirable changes in body composition, strength, and sexual function begin to occur." (Finkelstein 2013)

Yep, that is the study you don't not want to be part of, but....

I bet you will still be interested in the results. Am I right? Ok, let's see then. In men receiving goserelin acetate (kills the natural testosterone production) and 0 g (pla­cebo), 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel daily (cohort 1), the mean testosterone levels were
  • 0g testosterone: 44±13 ng per deciliter, 
  • 1.25g testosterone: 191±78 ng per deci­liter
  • 2.5g testosterone: 337±173 ng per deciliter, 
  • 5g testosterone 470±201 ng per, and
  • 10g testosterone 805±355 ng per deciliter
With 1.4 pg per milliliter, 7.9±2.9 pg per mil­liliter, 11.9±5.7 pg per milliliter, 18.2±10.2 pg per milliliter, and 33.3±15.3 pg per milliliter the estrogen levels of all participants were all well within the normal range (<55pg/ml).
Update: As Dr. Crisler (www.allthingsmale.com) just told me the accuracy of the information about estrogen may be questionable, because the essay the scientists used is not reliable in adult men. Instead, he suggest you use a "sensitive" essay like LabCorp (#500108), which uses the "cutting edge" LC/MS technology, Mayo Clinic's "Enhanced Estradiol" (#81816) or LabCorp's "Sensitive Estradiol (#140244), which is less expensive and thus probably a good choice for those without insurance. Dr. Crisler also pointed out that the wide variations you see in T-levels are actually a "very good thing, since this more closely mimics the serum profile of young healthy men". I do not deny that, but I still thought that it was wise to point out that the difference between 805ng/dl and 924ng/dl is absolutely non-significant when you have a range of ±521ng/dl.
Now the latter was obviously true for the guys on the aromatase inhibitor as well, with 1-2pg/ml their levels were however pathologically low and considering the high standard deviations, their T-levels were not that much higher:
Figure 1: Testosterone (ng/dl) and estrogen (pg/ml x10) in healthy men on 0, 1.25, 2.5, 5 and 10g (T0-T10) of testosterone gel with and without an additional aromatase inhibitor (Finkelstein. 2013)
"In men who also received anastrozole (cohort 2), the corresponding mean testosterone levels were 41±13 ng per deciliter, 231±171 ng per deciliter, 367±248 ng per deciliter, 485±240 ng per deci­liter, and 924±521 ng per deciliter and the corresponding mean estradiol levels were 1.0±0.4 pg per milliliter, 1.2±0.4 pg per milliliter, 2.0±2.3 pg per milliliter, 2.1±1.9 pg per millili­ter, and 2.8±1.8 pg per milliliter." (Finkelstein 2003)
[*please note the high (up to 50%!) standard deviations which tell you that the response to transdermal testosterone may vary profoundly from one men to another]
If you take a closer look at the data in Figure 1 and keep in mind that I had to multiply the estrogen levels by x10 in order to fit them into the same graph, it becomes all the more evident that the men in the non-AI group all had normal (<55pg/ml) estrogen levels. Their peers in the anastrazole group, on the other hand, had basically no estrogen at all and correspondingly high testosterone to estrogen ratios. In the worst case (yep, that is something bad!), namely 10g of t-gel + A,I the latter was as high as 335, which is almost 12x higher than in the 2.5g testosterone group without anastrazole (cohort 1).

No T, but tons of body fat

Apropos, cohort 1, in this group of men those who received the anti-androgen goserelin alongside a low(ish) doses of T-gel, i.e. either 0 g, 1.25 g, or 2.5 g of testosterone, daily, had significantly higher body fat levels and those in the 0 and 1.25g of T-gel significantly lower levels of lean mass compared to their peers in the 5g T-gel per day group.

Just a reminder: The testosterone level of the guys in the 5g group was only 470ng/dl and thus still rock bottom - the age adjusted normal levels for men are after all (I highlighted the group, where most of the subjects were in):
  • Effects of high and low testosterone on body composition (learn more)
    14-15 yr: 33-585 ng/dL
  • 16-17 yr: 185-886 ng/dL
  • 18-39 yr: 400-1080 ng/dL
  • 40-59 yr: 350-890 ng/dL
  • > 60 yr: 350-720 ng/dL
Those on the highest dose of T-gel (10g) ended up at the top (remember the standard deviations) of the normal range for testosterone and right in the happy medium for estrogen (normal range is 14-55pg/ml). These guys  experienced a significant decrease in body fat and increases in tigh muscle area and leg press strength.

Interestingly, both the decrease and increase in body in response to high and low testosterone levels occurred almost exclusively in the "benign" subcutaneous adipose tissue. The intra-abdominal­ fat area, on the other hand did not change significantly in any group. If we follow the standard interpretation of the health effects of the different body fat stores, the conclusion would thus be that low T is not so much of a problem, after all it's all "healthy fat" that you will gain... to bad that too much of that "healthy fat" will make you just as insulin resistance as the visceral fat - it just takes longer for the negative effects to occur.

Now what did the AI do?

Suggested read explaining why the annihilation of E2 has negative effects on your body comp: "Estrogen, Friend or Foe of Muscle Hypertrophy? Plus: Are You 'SERMing' Away Your Satellite Cells?" | more
I know, the most intriguing question has not been answered yet: What was the role of anastrazole in all this? And how did the subjects in cohort 2 fare compared to their "high" (remember even the 10g guys had normal estrogen levels) estrogen counterparts. Well,...
"In cohort 2, the percentage of body fat increased in all groups when the aromatization of testosterone to estradiol was inhibited. The magni­tudes of these increases were similar with doses of 0 g, 1.25 g, 2.5 g, and 5 g of testosterone daily, a finding that suggests a predominantly estro­genic effect" (Finkelstein. 2013)
Yep, I deliberately quoted this, because I know that you've been brain-washed to believe the opposite would happen. The big bad estrogen is what keeps you lean... good that you have been taking natural AIs for years, right? Well, no obviously not. Probably rather the reason that you still don't have the cover-model look you are aspiring.

Did you know that (a) the endogenous production of estrogens has significant protective effects on your heard cardiovascular health (Sudhir. 1999) and that (b) aromatase is neuroprotective and low levels of it have been associated with the occurance + progression of neurological diseases such as dementia, Alzheimer's and Parkinsons as well as an inability to recover from mechanic (trauma) or chemical (intlammation) damage to the brain (Azcoitia. 2001)? No? Well, let's hope that this is because you've never heard it and not because you've been abusing AIs for the past decade ;-)
So, to use an AI or not - is that even a question? A direct comparison of all the data from cohort 1 (no aromatase inhibitor) and cohort 2 (using anastrazole), informs us that
"The cohort–testosterone dose interaction was significant for the percentage of body fat (P = 0.001), intraabdominal­fat area (P = 0.021), subcutaneous ­fat area (P = 0.029), sexual desire (P = 0.045), and erectile function (P = 0.032)" (Finkelstein. 2013)
Or, to put it another way: The study shows us that estradiol exerts an inde­pendent effect on body fat, sexual desire and erectile function. So you better don't ignore the real world implications you are about to suffer, when you put too much faith in hearsay instead of looking at your actual blood levels:
"In the groups that received testosterone, inhibi­tion of estrogen synthesis (cohort 2), as com­pared with intact estrogen synthesis (cohort 1), was associated with significant increases in the percentage of body fat (P<0.001), subcutaneous­ fat area (P<0.001), and intraabdominal­fat area (P = 0.002) and with significant decreases in sexual desire (P<0.001) and erectile function (P = 0.022)" (Finkelstein. 2013)
Yes, you heard the scientists right. Suppressing your estrogen levels is going to make you fat, rob you of your sexual desire and render you unable to perform the deed.

At the same time it had no beneficial effect on the increases in lean body mass or strength or any other positive outcome the subjects got from using T-gel. On the contrary, the low estrogen levels on in the 10g T-gel group did actually blunt reduce the lean mass gains and the fat loss the men in cohort 1 (no anastrozole) experienced, when they used 10g of T-gel per day was effectively reversed by the AI.

Figure 2: Fat gain, lower lean mass gain, less sexual desire & lower sexual function (not shown) and the list goes on... there really is nothing remotely beneficial about low estrogen (figures from Finkelstein. 2013).
It should thus be absolutely obvious that the only reason you should use an aromatase inhibitor with your testosterone replacement therapy is blood work that indicates that you have serious issues with over-aromatization. In many cases those can be reduced if not solved by (a) reducing inflammation and (b) getting rid of your belly.

To deliberately annihilate your estrogen levels, on the other hand, is simply stupid - irrespective of whether you are on TRT or not and even if you don't care about the negative long-term effects on your brain and heart health.

References:
  • Azcoitia I, Sierra A, Veiga S, Honda S, Harada N, Garcia-Segura LM. Brain aromatase is neuroprotective. J Neurobiol. 2001 Jun 15;47(4):318-29.
  • Sudhir K, Komesaroff PA. Clinical review 110: Cardiovascular actions of estrogens in men. J Clin Endocrinol Metab. 1999 Oct;84(10):3411-5. Review.

Eat Whole Foods! Lose Weight, Improve Your Blood Lipids, Reduce Estrogen, Protect Yourself Against Chromosomal Damage and Defeat Prostate Cancer With Cabbage.

Image 1: The magic ingredient is in the root not in the commonly eaten leaves of "bok choy". Chances that you will find a "whole" (including the root) chinese cabbage" (lat. brassica rapa) at your local supermarket, are yet very low... but wouldn't this be a good reason to start gardening really "whole" foods in your backyard? (img. Wikigardener)
If you are a student of the SuppVersity, you are probably already annoyed by my favorite slogan "Nature knows best!" Nevertheless, I will not tire to repeat that "eating your way to a leaner and healthier you" is probably the only sustainable alternative on a side-effect ridden life on drugs such as Xenical.

As Trisha Gura points out in a newsitem on sciencemag.com,
[t]he current trio of [weight loss] drugs on the market, endocrinologists say, is, at best, weak and, at worst, plagued by side effects. Hoffmann-La Roche's Xenical, for instance, blocks fat-digesting enzymes called lipases. That prevents the gut from digesting and absorbing fat. But lipids aren't the only molecules malabsorbed; Xenical also causes cramping and severe diarrhea in many obese patients because water molecules also fail to be taken up by the gut.
Thus, the study results of Sojin An and his colleagues from five different research centers in the Republic of Korea, which although they have been published back in 2009, landed in my inbox only recently, come along quite handy. In a 8-week controlled trial the scientists found that the addition of 50mg/kg of an ethanolic extract from Brassica campestris spp. rapa roots (human equivalent: 4mg/kg) to the high fat diet (+25% more calories than standard chow) of ICR (imprinting control region) mice did not only ameliorate the weight and fat gain, but even reduced both gains in body weight (-3%), as well as white adipose tissue weight (-8%) compared to the normal fed control group.
Figure 1: Weight gain, fat gain (white adipose tissues) and energy intake of mice on a hypercaloric high fat diet (HFD) supplemented with either 50mg/kg chinese cabbage root extract or Orlistat (Xenical); values expressed relative to control group on normal chow (data calculated based on An. 2009)
The cabbage root extract outperformed Xenical not only in terms of its effect on body weight and fat accumulation, other than the pharmacological fat-blocker, it also preserved the leptin sensitivity of the mice, which was profoundly compromised (as can be seen by the +25% increase in leptin) in the Orlistat group (cf. figure 2).
Figure 2: Relative changes in blood lipids and adipokines in mice on a hypercaloric high fat diet (HFD) supplemented with either 50mg/kg chinese cabbage root extract or Orlistat (Xenical); values expressed relative to control group on normal chow (data calculated based on An. 2009)
The underlying mechanism behind all that is probably related to the 2-fold increase in beta-3 adrenergic receptor and the 3-fold increase in hormone-sensitive lipase (HSL) gene expression the researchers measured in the white adipose tissue of the animals. Both of them are intricately involved in the breakdown and release of stored triglycerides and their expression in rodents is suppressed upon high fat feeding.
In case you are as annoyed as I would be by the branding in the figures, I suggest you tell my friend "The Press" over at Anabolic Minds that "copy + pasting" the work of others like that, instead of citing only parts of the article and linking back to the source, is not what one would expect of an "anabolic mind". Thanks!
Want to plant your own veggies, but don't know how? Listen to SHR #703 "Urban Gardening: Like Your Life Depends On It"
My repeated advice to "eat whole foods", gets a whole new meaning, however, when you further consider that
  • fatty acids from the pollen of brassica campestris have been shown to have a "strong inhibitory" effect on aromatase (Yang. 2009),
  • the leaves protect "against in vivo genotoxicity and oxidative stress" (Tiku. 2008), and
  • the chloroform extract from its pollen kills prostate cancer cells (Wu. 2007),
doesn't it? There is yet one obvious caveat to this advice. Without a green thumb, as Carl Lenore's significant other, Alisa Profumo, has one, it will be hard to get your hands on a whole brassica campestris plant, i.e. its leaves, roots and the pollen-laden blooms... ah, and just in case you take this insight as an opportunity to start gardening, I suggest you go and check out episode #703 of Super Human Radio "Urban Gardening: Like Your Life Depends On It" - who knows, one day your life could actually depend on it ;-)

Melatonin As Potent as Letrozole in Inhibiting Aromatization of Testosterone to Estrogen - This Raises the Question: Is a Lack of / Bad Sleep to Blame for Breast Cancer?!

Sleeping for 7-8h w/out interruption in a pitch black room to max. your melatonin is the best breast cancer prevention.
It may sound hilarious to the next best average Joe, but the study results Suthat Chottanap and colleagues from the Chulabhorn Graduate Institute are about to present in one of the next issues of Toxicology in Vitro confirm what SuppVersity readers already knew: It's more than likely that there is a direct link between a lack of quality sleep as people who are working shift works have it and the risk of breast cancer.

The latter increases in women who do not sleep during the period of the night when melatonin levels are typically at their highest by ~14% (Davis. 2011), an observation that appears only logical in view of what I am about to tell you today.
You can learn more about sleep and the circadian rhythm at the SuppVersity

Sunlight, Bluelight, Backlight and Your Clock

Sunlight a La Carte: "Hack" Your Rhythm
Breaking the Fast to Synchronize the Clock

Fasting (Re-)Sets the Peripheral Clock

Vitamin A & Caffeine Set the Clock

Pre-Workout Supps Could Ruin Your Sleep
Among various naturally occurring, biologically active compounds, resveratrol and melatonin have been suggested to act as aromatase inhibitors, which make them potential candi-dates in hormonal treatment of breast cancer.

These previous observations were the actual reason why Suthat Chottanap and colleages set up a handful of petri-dishes in which they a co-culture model primary human breast adipose fibroblasts (BAFs) with testosterone and melatonin or resveratrol. It has long been known that these fat cells from the breast tissue can convert testosterone to estradiol, and do thus contribute to the estrogen receptor-mediated growth and proliferation of of breast cancer T47D cell proliferation.
Figure 1: Anti-aromatase effect of resveratrol vs. melatonin (1000x lower dosage; left) and anti-proliferative (=anti-growth) effects of melatonin in breast cancer cells (Chottanapund. 2014)
As the data in Figure 1 shows, this nasty side effect of the presence of testosterone and the fat aromatase factories, the BAFs, was countered by both melatonin and resveratrol, albeit at different levels of the "drug".
  • for resvertrol the scientists needed a concentration of 20µM, i.e. 20 microMol = 0.000002 Mol and thus 1000x more(!) than for melatonin
  • for meltonin a concentration of 20nM, i.e. 20 nanoMol = 0.000000002 Mol was sufficient
Now that alone is pretty astonishing. In the end, you could argue, however, that it would only confirm what we already knew: Resveratrol is a much less potent "wonderdrug" than the hype in mainstream media makes it look like.

What really makes the results outstanding, though, is that melatonin was as potent as letrozole, the most potent antiaromatase inhibitor the publicly available pharmaceutical arsenal knows in suppressing cell proliferation, estradiol (E2) production and gene expression of CYP19A1, pS2andKi-67. No wonder that the Thai authors of the paper at hand are convinced that "melatonin clearly offers potential advantages for breast cancer treatment". And this assumption is supported by both the often-reported association between increased breast cancer risk and shift work and the inverse correlation between the risk of breast cancer and urinary melatonin levels Eva S. Schernhammer and Susan E. Hankinson report in a 2005 paper - a correlation, which remained significant even when the women who had a history of night-shift were excluded!
Learn how light synchronizes your circadian rhythm and protects you against breast cancer & obesity.
Bottom line: It's too early to tell anyone to consume melatonin supplements as an effective means to counter the development of breast cancer. The results of the study at hand do yet confirm that sleep and in that sleep during a time of maximal melatonin production, which is at night or in a pitch black room is of paramount importance to your health.

While we are waiting for the first rodent and human studies to confirm a systemic anti-aromatase effect of melatonin, I would thus suggest that you take another look at the SuppVersity Circadian Rhythm Series, all the articles of which you can find @ http://suppversity.blogspot.com/feeds/posts/summary/-/crs/?max-results=9999 if you are using an RSS compatbile browser or a plugin for chrome.
References:
  • Chottanapund, Suthat, et al. "Anti-aromatase effect of resveratrol and melatonin on hormonal positive breast cancer cells co-cultured with breast adipose fibroblasts." Toxicology in Vitro (2014).
  • Davis, Scott, Dana K. Mirick, and Richard G. Stevens. "Night shift work, light at night, and risk of breast cancer." Journal of the national cancer institute 93.20 (2001): 1557-1562.
  • Schernhammer, Eva S., and Susan E. Hankinson. "Urinary melatonin levels and breast cancer risk." Journal of the National Cancer Institute 97.14 (2005): 1084-1087.

Chest Fat, Bitch Tits, Chesticles, Gynecomastia, Lipomastia and Co.: Infinite Ways to Name it, Only 5 to Get Rid of It

Image 1: Is it what he eats, is it what he drinks or is it just  andropause? Whatever it may be, Jack does not have the "classic gyno".
In the last installment of this two-part series on gynecomastia, lipomastia and co. we have seen that the number of appellations this common, mostly benign enlargement of the male breast has been given, is easily outnumbered by the potential, mostly pharmacological, but also supplemental and/or dietary factors which have been implicated in its development. In a recent paper, Krysiak and Okopien estimate the incidence of mild proliferation of the glandular breast tissue to 30%-50% of the male population (Krysiak. 2012). Against that background, the universal ignorance towards the profound psychological effects, as well as the tacit acceptance that, breasts or no breasts, "men don't cry" are certainly uncalled-for.

If it's benign you got to live with it!

The idea, "if it's not cancerous", it won't hurt, is probably also the main reason for the lack of viable (N=5), let alone "proven" (N=1, surgery) treatment strategies. A couple of case-reports and small scale studies do yet suggest that its surgical removal, which is uncertainly the method of choice for non-benign or exuberantly proliferating tissue growth, is not the only option you may have to get rid of a condition of which I suspect that it has been bothering many of you for years now.

Whichever of the following strategies you may pick, your first step should always be to avoid / drop all of the 45+ offenders I mentioned in the last installment, and to avoid the 10 previously discussed anti-androgens like a plague. Yet while these "passive" treatments may suffice to stop your breasts from growing even further, it is unlikely that they will put a long lasting real gyno (not just normal fat!) in remission. If you are among these unfortunate, yet certainly not rare cases, you may have to resort to one or more of the following "alternative" (from the perspective of most MDs) but not mutual exclusive anti-gyno strategies.

Getting rid of "gyno" by losing body fat (not weight!)

Image 2: This poor boy may not know it, but he is just lying the fat foundation for embarrassing female breasts
It should actually be obvious that losing excess body fat is the logical next step following aforementioned necessity to avoid anything that could precipitate gyno. Aside from the constant assault to xeno- (BPA & co=)and purportedly healthy phyto-estrogens (soy & co), the obesity epidemic is probably the main reason for the high prevalence of enlarged breast tissue in the male part of the population, anyways. Particularly during puberty, when the natural hormonal production overshoots the increased aromatase activity in the abundant adipose tissue of today's Playstation gambling couch potatoes can be hazardous.

Puberty and the spontaneous regression of pubertal gynecomastia can yet also serve as an encouraging example that an ample increase and stabilization in the androgen to estrogen ratio, as it should occur towards the end of puberty, can send mild cases of pubertal gynecomastia and lipomastia into remission. Similar effects can be seen in adults, when
  • you lose fat without starving yourself - Starvation would lead to decreased androgen production and could, if anything, help not to make things even worse; more often than not, it does yet make things worse. After all, large breasts on a skinny man look even worse than breasts of the same size on a slightly chubby guy.
  • you are gradually losing fat over a long period of time - It is more than likely that the chest fat is going to be the last to go; in fact, it may take a profound reduction in total body fat shift the androgen-to-estrogen ration into the normal range before you see any improvements
  • you don't resort to questionable fat burners - with herbs, tea or whatever extracts in them that will have either direct estrogenic or anti-androgenic side-effects or mess with the cytochrome P450 cascade of your liver (see previous installment)
Fat loss is a particularly good tool to get rid of "fat tits", i.e. an unbalanced deposition of regular fat tissue. It will take its time, though, and it won't help to combat "acute flare-ups" from the (obviously accidental) ingestion of certain "supplements". It is likewise unrealistic to assume that it would put a full-blown gynecomastia, i.e. the (over-)growth of glandular tissue, cancerous or not, into remission.

Getting rid of "gyno" with Tomaxifen, a selective estrogen receptor inhibitor

In view of its kinship with breast cancer, it should not surprise you that the single scientifically well-established anti-gyno agent is a selective estrogen receptor modulator, in short SERM. Tamoxifen, brand name Nolvadex, has been used in a couple of small scale trial with reasonable success (e.g. Parker. 1986; Algaratnam. 1987; McDermontt. 1990; Ting. 2000), the results of which Braunstein et al. summarize as follows (Braunstein. 2007):
[A]dministered orally at a dose of 20 mg daily for up to 3 months, has been shown to be effective in randomized and nonrandom-ized trials, resulting in partial regression of gynecomastia in approximately 80% of patients and complete regression in about 60%.
Despite the existent evidence that would support the use of Tamoxifen as the "anti-gyno" drug of choice, Daughty and Wilson, in their 2003 letter to the editor of the British Journal of Medicine, rightly state:
The evidence base for their conclusion is small (135 patients) and is certainly not derived from randomised controlled clinical trials. [...] until more evidence shows that tamoxifen is safe in this condition it should not be recommended as first line treatment, especially in pubertal boys.
If you add to that the potential hepatoxicity (cf. "Milk Thistle Against Tamoxifen Induced Liver Injury"), as well as the two documented cases of epigastric distress and the one known case of  post-traumatic deep-vein thrombois, it is self evident that you and your medical practitioner should carefully monitor your liver as well as other health parameters if you decide to give Tamoxifen or alternatively Clomiphene (cf. Plourde. 1983) a try.

Getting rid of "gyno" with  aromatase inhibotors

There is also some evidence from case reports that would support the use of 2nd generation aromatase inhibitors (AI), Letrozole, in particular, to combat gynecomastia. As Braunstein et al. point out (Braunstein. 2007), their efficiency seems yet to be limited to cases, where over-aromatization of testosterone into estrogen is the underlying reason of the the problem. If this applies to you, talk to your medical practitioner about the use of a very low dose of letrozole, like 2x per week 2.5mg, or resort to 25mg of the (in the US formerly) OTC, yet very potent aromatase inhibitor ATD (more is counter-indicated because it could start "clogging" your androgen receptor, cf. "Antiandrogen effects of ATD").
Note: In a 2004 randomized controlled trial by Plourde et al. the "standard AI", Anastrazol, was ineffective for patients with residual pubertal gynecomastia (Plourde. 2004). Similarly, Riepe et al. found no effects in pubertal boys other than a reduction in breast tenderness (Riepe. 2004). It is therefore, as Sarah L. Maidment points out not not just that "Anastrozole may not be more effective than placebo in decreasing the size or volume of breast tissue in persistent pubertal gynaecomastia", but also that "its long-term effects and safety are still unknown" (Maidment. 2010). 
If the over-aromatization is related to an increased amount of body fat, this treatment strategy should be complemented by appropriate lifestyle changes (diet + exercise; follow the SuppVersity for daily tips on what works). The effectiveness of your weight loss efforts will be largely augmented by the restoration of a normal estrogen-to-androgen ratio and will hopefully allow you to maintain the latter once you seize taking the drug.

Update: If you hesitate to use a "real" aromatase inhibitor you could also resort to melatonin (kudos to Peter Rouse for the reminder), of which a dose as low as 3mg melatonin per day taken at 5pm for 6-month can shift the testosterone-to-estrogen ratio into the desired direction (Luboshitzky. 2002)

Getting rid of "gyno" with topical DHT cream

Largely unknown in the US, but a relatively common treatment strategy in Europe, in particular in France, is the use of topical DHT cream. The available literature on this issue is scarce. The results of one of the few well-documented trials by Kuhn et al. are yet promising and stand in line with the natural "anti-estrogenic" effects of dihydrotestosterone (Kuhn. 1983):
Local administration of DHT was followed by the complete disappearance of gynaecomastia in 10 patients, partial regression in 19 and no change in 11 patients after 4 to 20 weeks of percutaneous DHT (125 mg twice daily).
This is a 33% success rate in patients with idiopathic (meaning we don't know the underlying reason) gynecomastia. That is less effective than tamoxifen  and certainly neither what you would call a "tried and proven" method, but probably better than the bro-scientific use of DHT-precursors and pro-steroids with structural resemblance to DHT. Especially in the US, it may however difficult to find a medical practitioner who would be willing to prescribe and monitor this treatment, I guess.

Conclusion and the last resort: Surgery

Image 3: Assuming that you find a surgeon who knows what he is doing, surgery is unquestionably the best - diet and exercise aside, probably also the safest treatment strategy. In cases of non-benign gynecomastia it should be the go-to treatment, anyway.
If we take a final look at the meager amount of treatment options, it stands to reason that the avoidance of anything that could exasperate the condition, as well as the reduction of body fat should have priority over all other treatment strategies. If those fail, the next step should be a comprehensive hormonal panel, on the asis of which you and your medical practitioner should decide which route to go.

In case none of the pharmacological approaches works, you can still resort to to surgery (or radio-therapy, but I guess most of you will prefer the knife, right?), the "gold standard therapy for symptomatic gynecomastia in most patients" (Johson. 2011). Just make sure you do not spoil the ship for a ha'porth of tar - or put more simply, go and seek an expert!

5α-androstane-3,6,17-trione - Kneller's Trione: Newly Patented Aromatase Inhibitor that Raises Testosterone Without Lowering Estrogen Levels!?

I happened onto an interesting patent (Kneller. 2011), published on 02/10/2011 the author of which, Bruce Kneller, who was arrested in the course of a steroid bust back in 2006, claims to have invented an aromatase inhibitor, 5α-androstane-3,6,17-trione (Kneller's Trione) which produces "substantial and significant increases in plasma testosterone levels in men while inducing no changes outside the accepted normal limits for plasma estradiol levels". This is very different from your usual AI (ATD, Arimidex, Letrozole, etc.) which tend to eradicate estrogen and thus produce nasty side effects. As far as its concrete applications are concerned the author writes:
The oral, daily dose of Kneller's Trione can be from about 25 mg to about 750 mg per day, such as, for example, from about 25 mg to about 500 mg per day, from about 25 mg to about 250 mg per day, or from about 25 to about 100 mg per day. [...] In some embodiments of the invention the composition comprising Kneller's Trione is formulated as a tablet, capsule, caplet, powder, suspension, gel preparation, aqueous solution, solid food form (e.g., chewable bar or wafer), or liquid dosage form such as elixirs, syrups, dispersed powders, granules or emulsions.
Bruce W. Kneller then cites a pilot study in which Kneller's Trione was administered orally to three individuals at dosages of 25mg, 50mg and 100mg.
Figure 1: Tables from patent of Kneller's Trione
As can be seen from the tables in figure 1 the effect of 5α-androstane-3,6,17-trione depends on a) previous hormone levels and b) dosage. Most interestingly administration of 50mg Kneller's Trione to subject 2 who had low estradiol levels to begin with did not reduce these levels any further. With reference to the optimal dosing scheme and potential side effects Kneller reports:
Although dosing of Kneller's Trione went as high as 750 mg per day in this pilot study, no added benefits were seen with dosages this high. Dosages of 250 mg and 500 mg per day also raised total testosterone and bioavailable testosterone levels substantially and safely but did not seem to offer any added benefit over a dose of 100 mg per day. At the 750 mg per day oral dosing level, occurrence of a priaprism caused the subject to withdraw from participation in this pilot study. No other adverse events were noted by any study subject during this pilot study. Observations of every subject's liver function, kidney function, blood lipid levels, blood pressure, heart rate, respirations, and body temperature were made at frequent intervals during this pilot study and were found to be within medically established normal ranges and values.
While my cursory web-search for available OTC supplements with this product did not produce any results, I assume it won't take long until we see a range of these products on the market - even in view of the fact that a constant boner (priapism) may not be the worst, but certainly an annoying and in the long run painful side effect ;-)

As always, I will inform you as soon as there are more recent study results and or product releases. In view of the fact, that Kneller is also the patent-holder of the "OUTLAST" formula in Gaspari Nutrition's cell-volumizer SizeON it's most likely that we will see a "new Novedex XT" hit the market soon.

Edit: Kevin just posted a comment mentioning, he believes that it is already in "some Gaspari products" and in fact. He is right! Its part of Gaspari's Halodrol MT, which I believe is not produced anymore, though. Well, I assume that's what happens to things which work, these days...