Showing posts with label clomiphene. Show all posts
Showing posts with label clomiphene. Show all posts

Wednesday, June 17, 2015

Clomiphene Citrate, Overlooked Testosterone Replacement Therapy (TRT) Alternative? 2.5x Higher T, No Side Effects

Can you replace androgel or injectable T with regular chlomiphene citrate tablets? Or is this just "broscience"?
While many of the things people will tell you about the negative side-effects of testosterone replacement therapy (TRT) are scientifically questionable, un- or even disproven, there's one nasty side effect that is simply unavoidable: the decline in natural testosterone production. Needless to say that this is why natural testosterone boosters, i.e. products that contain (natural) ingredients that may boost your own endogenous testosterone production, are so popular. Unfortunately, these pills have a larger impact on their manufacturers revenue than your T-levls. If they even work, the meager 20%-30% T increase they have to offer is simply not enough for someone whose testosterone level hovers at <250 ng/dl and thus 50ng/dl below the "low T" cutoff.
Higher T levels won't build tons of muscle on its own, but it will make these more effective:

Tri- or Multi-Set Training for Body Recomp.?

1, 2, or 5 sets per Exercise? What's "best"?

Pre-Exhaustion Exhausts Your Growth Potential

Full ROM ➯ Full Gains - Form Counts!

Battle the Rope to Get Ripped & Strong

Study Indicates Cut the Volume Make the Gains!
It's not enough to bring someone with a low testosterone production back into the normal or upper normal range; the place, where all of us would like to be - and that's exactly, where studies indicate clompiphene citrate may come in.

10 years ago, Shabsigh and his colleagues from the NY Presbyterian Medical Center investigated the effects of 25mg of clomiphene citrate per day in 36 Caucasian men with hypogonadism )defined as serum testosterone level less than 300 ng/dL).
Figure 1 : Pre-/post testosterone, estrogen and T/E ratio in the 27-60-year old subjects before and after taking a low dose of 25mg clompiphene citrate per day for 4-6 weeks (Shabsigh. 2005) | the bars in the graph show relative values (control = 100%), the figures on top are absolute values in the units shown below each bar).
As you can see in Figure 1, the testosterone levels of the 27-60-year old subjects, which were 247.6 ± 39.8 ng/dL respectively, had risen by a whopping 146% to  610.0 ± 178.6 ng/dL at the first follow-up visit (4–6 weeks). Due to the fact that SERMs are recognized as estrogens by the body, the aromatase from testosterone to estrogen didn't increase to the same extent. Accordingly, the T/E ratio improved as well - from 8.7 to 14.2 (P < 0.001 | that's 60.9%), to be specific.
What is clomiphene citrate? Clomiphene citrate is a selective estrogen receptor modulator that was developed to stop estrogen dependent breast cancer growth. The way the molecule binds to the estrogen receptor without fully initiating the pro-estrogenic signalling cascade is yet also interesting for men, because in men estrogen is the #1 negative feedback factor. This means when estrogen levels are high and the receptors in the brain are free to dock to, your body will think "hmm... if there's so much estrogen floating around and estrogen can only be produced (in men) if its derived from testosterone by aromatization, there must be plenty of testosterone, so let's shut down the production." Well, ok, that's not a scientifically accurate description, but I guess you get how it works. If the SERM blocks the receptor the negative feedback is shut down and the testosterone production can flourish.
Very similar results were observed in a cohort of 990 men who presented with sexual dysfunction who received a similar total dose of clomiphene citrate, but as 50mg taken every other day. What is particularly interesting about this, study, though, is that (a) not all subjects even had "low" (by definition) T-levels and that (b) the restoration of normal or even normal-high testosterone levels did not, as some of you may expect, restore the subjects messed up sexual function. Especially in the older subjects, other organic reasons (e.g. atherosclerosis, diabetes, etc.) may have blunted the beneficial effects of T.
Figure 2: Effect of 50mg clomiphene citrate eod on sexual function (responder = restored, etc.) stratified for age (left) and testosterone response stratified (right | Guay. 2003)
That's not enough? Well, almost identical results have been reported by Ioannidou-Kadis (2005), Whitten (2006) and Kaminetsky et al. (2009 & 2013); and Hussein et al. (2005) even recommend clomiphene citrate administration for cases of nonobstructive azoospermia.

Now you will probably be asking for side effect, right? Well, all of the previously cited studies report none of the often heard of side effects that occur on the high doses in post-cycle therapy of steroid using athletes like distorted vision or impaired blood lipids. And a 2012 study by Moskovic et al. found no physiological or psychological side effects, either. That's why I wouldn't overrate either the reports of debilitating physiological side effects on the boards or the three existing case reports about psychotic episodes in men with pre-existing psychological issues on clompiphene citrate (Knight. 2015).
Table 1: While the testosterone levels will increase even if you're sick (having diabetes and hypertension) the beneficial effects on sexual function are blunted in men with endothelial or metabolic disease (Guay. 1995).
What I would take into consideration, though is the following caveat: Clomiphene works only in men whose natural testosterone production is still intact. If your T-levels are low, because there's a physiological problem with your testes (as it often occurs when you age | Tenover. 1991) or hypothalamus, it won't work, because even if clomiphene takes away the negative feedback estrogen exerts in the "hormone production control center" in your brain, this will increase the T- production onl if the "center" and your testes are both functioning properly.
Figure 3: While clomiphene won't help people who don't produce enough testosterone because their testes or hypthalamus are malfunctioning, there's good evidence, for example from a 2012 study by Katz et al., that proves that it will restart the endogenous testosterone production of chemical athletes (Katz. 2010).
So what? Is it an alternative? Well, let me cite Frederick Taylor and Laurence Levine who compared clomiphene citrate (CC) and regular testosterone gel replacement therapy (TGRT) in their 2010 study and conclude that "CC represents a treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT" (Taylor. 2010). And that's not all, clomiphene citrate was cheaper (83$ vs.  $265 per month) and again, "[t]here were no adverse events reported" (Taylor. 2014) in any patients at the 8–40 month follow ups. What remains to be sees is what will happen if you're "on" for 10 years.

CC will yet only work if your testes & HPT work. Otherwise, TRT is is the only option to get back to normal testosterone levels. For people whose T levels are suppressed for other reasons (e.g. steroid abuse | Figure 3), it's a viable alternative - in the medium to short run | Comment on FB!
References:
  • Guay, ANDRE T., S. U. D. H. I. R. Bansal, and GERALD J. Heatley. "Effect of raising endogenous testosterone levels in impotent men with secondary hypogonadism: double blind placebo-controlled trial with clomiphene citrate." The Journal of Clinical Endocrinology & Metabolism 80.12 (1995): 3546-3552.
  • Guay, A. T., et al. "Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?." International journal of impotence research 15.3 (2003): 156-165.
  • Hussein, Alayman, et al. "Clomiphene administration for cases of nonobstructive azoospermia: a multicenter study." Journal of andrology 26.6 (2005): 787-791.
  • Ioannidou-Kadis, Stella, et al. "Complete reversal of adult-onset isolated hypogonadotropic hypogonadism with clomiphene citrate." Fertility and sterility 86.5 (2006): 1513-e5.
  • Moskovic, Daniel J., et al. "Clomiphene citrate is safe and effective for long‐term management of hypogonadism." BJU international 110.10 (2012): 1524-1528.
  • Kaminetsky, Jed, and Micah L. Hemani. "Clomiphene citrate and enclomiphene for the treatment of hypogonadal androgen deficiency." Expert opinion on investigational drugs 18.12 (2009): 1947-1955.
  • Kaminetsky, Jed, et al. "Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel." The journal of sexual medicine 10.6 (2013): 1628-1635.
  • Katz, Darren J., et al. "Outcomes of clomiphene citrate treatment in young hypogonadal men." BJU international 110.4 (2012): 573-578.
  • Knight, Julia C., et al. "Clomiphene-Associated Suicide Behavior in A Man Treated for Hypogonadism: Case Report and Review of The Literature." Psychosomatics (2015).
  • Shabsigh, Ahmad, et al. "Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism." The journal of sexual medicine 2.5 (2005): 716-721.
  • Tan, Robert S., and Deepa Vasudevan. "Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse." Fertility and sterility 79.1 (2003): 203-205.
  • Taylor, Frederick, and Laurence Levine. "Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost." The journal of sexual medicine 7.1pt1 (2010): 269-276.
  • Tenover, Joyce S., and William J. Bremner. "The Effects of Normal Aging on the Response of the Pituitary‐Gonadal Axis to Chronic Clomiphene Administration in Men." Journal of andrology 12.4 (1991): 258-263.
  • Whitten, Scott J., Ajay K. Nangia, and Peter N. Kolettis. "Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate." Fertility and sterility 86.6 (2006): 1664-1668.

Saturday, September 22, 2012

Fighting Body Fat W/ Green Tomatoes; Fasting, Exercise & Cognitive Performance; Potassium Citrate & Coconut Oil Strengthen the Bone; 25mg Clomid Double Testosterone

Image of the week: Golf-ball sized tumors from GMO corn and a >100% increase in mortality in female rodents are the results of the (at least in Europe) much debated study by Gilles-Eric Séralini et al. (Séralini. 2012)
I must admit that I got somewhat bored with writing the same, or at least very similar introductions time and again. So I decided to start each and every installment of On Short Notice with either a picture or a figure that impressed, amused, enraged or, as in this case, shocked me, when I hit on it. The image you see on the right shows the rodents from the French GMO corn study that made the news earlier this week. Females, to be precise. With golf-ball sized mammary gland tumors. Nasty and the result of a life on a 22% GMO or 22% GMO + Round-Up diet ... yeah, you read me right: 22% was enough. In fact, "the rate of mortality [...] reach[ed] a threshold at the lowest (11%) or intermediate (22%) amounts of GM maize" (Séralini. 2012), already, and that irrespective of whether the corn was or wasn't treated with round-up.

Quite a difference to the previous 13 week rodent study, which was obviously enough for the officials to allow the Frankenfood to be sold as "save for human consumption". But enough of those nasty tumors and pre-mature deaths and on to a short collection of recent science news from the world of health, nutrition, supplementation and medication (exercise news will follow in a couple of days, don't worry ;-)



Red Tomatoes Are Good, But Green Ones Could Be Even Better - For weight Loss, At Least That's the simple message the results from a soon-to-be-published study on the AMPK- and PPAR-gamma mediated anti-obesity effects of 20 g/kg diet of red vs. green tomato water extracts (extraction took place at room temperature for 1h; Choi. 2012).

Figure 1: Significant benefits on weight gain, epididimal (=visceral) and liver fat were observed only with the dehydrotomatine, α-tomatine, trigonelline rich green tomato extract (based on Choi. 2012).
While both, the red (RTE) and green tomato extracts (GTE) did ameliorate the weight gain and fat accumulation of male C57BL/6 mice who received the RTE and GTE enriched chow after they had been pre-fattened on a "high fat diet" for 4-weeks, only the green tomato extract with its higher dehydrotomatine, α-tomatine and trigonelline extract had statistically significant effects on total body weight and visceral fat gain (see figure 1).

If you take a closer look at the photos of the rodents (small picture in figure 1), you will probably agree that judged by their physique the mice in the HFD + GTE appear to be the leanest. Now, it given the fact that "high" amounts of dietary fat and fatty livers are not exactly conducive to rodent health, the image may be misleading; and still, the fact that the purported "high fat" diet, had 4g more protein, 17g more fat and 23g less carbs per 100g, than the regular chow and thus a macronutrient composition of 24g / 41g / 24g makes me wonder if the control mice on the "healthy" low fat rodent chow would not have seen similar benefits from a few mg of GTE per day ;-)

As far as the underlying mechanisms are concerned the additional in-vitro experiments, Choi et al. conducted revealed that the anti-obesity effects were probably the result of concomitant increases of p-AMPK (to normal = control levels) and a profound suppression of the pro-adipogenic (=fat storage promoting) proteins PPAR-gamma, C/EBP-alpha and perillipin in the adipose tissue of the GTE treated animals. And with tomatine turning out to be the most potent (-80%) inhibitor of fat accumulation (vs. -10% for trigonelline), we eill probably soon see the first stanardized green tomato extracts being sold as dietary supplement. I mean, you all know how it works these days: If there is a single rodent study showing benefits, people will be willing to pay for it and since demand determines supply, it won't take long until you see the first 2xGTE based "fat burner" (featuring GTE as in green tea extract and GTE as in green tomato extract ;-) hit the shelves.



Regardless of whether you are low-carbing or not, eggs could literally give you a head-start in the morning (click here to learn more about the good "bad" eggs)
Breakfast Counters Mental Fatique, Exercise curbs appetite - Regardless of Whether You "Break the Fast" or Not! That's what a group of researchers from Korea found, when they analyzed the effects of consuming or omitting breakfast on the physical and mental fatique, as well as the cognitive task performance, mood and appetite ratings of twelve healthy male participants during and after four different test conditions:
  • no breakfast and rest, 
  • breakfast and rest, 
  • no breakfast and exercise and
  • breakfast and exercise
On each of the four test days the participants went through the 'same' routine that consisted of "breakfast (or continued fast), a 2 h rest, an exercise (treadmill run at 60% VO2max to expend ~710 kcal) or an equivalent rest period, a liquid snack, a 90 min rest period and finally an ad libitum lunch" (Veasey. 2012).

As I already mentioned in the title of this item, the mental fatigue ratings were significantly higher during the fasted compare to the fed trials. Correspondingly consuming breakfast prior to resting increased speed on a Rapid Visual Information Processing task (RVIP) - an effect that was not observed, when the breakfast was supplied after the exercise. The treadmill exercise lead to a significant reduction in hunger ratings during and even temporarily after the exercise, irrespective of whether or not the subjects had had breakfast. The effect was however more pronounced in the fed condition.

Recent UK study says: Children learn better w/ breakfast The findings of a study that used an online questionnaire + test system to establish a connection between breakfast consumption and cognitive performance in 1386 children aged between 6 and 16 years, from schools throughout the UK, appears to confirm previous laboratory studies, suggesting that breakfast can help maintain attention and memory during the morning (Wesnes. 2012).
Now, though all this clearly suggests that skipping breakfast was a very bad idea, I would like to remind you of the "priming" or "programming" effect I have outlined in my recent post on "breaking the fast". Against that background, the scientists' conclusion that "consuming breakfast before exercise decreased mental fatigue ratings following cognitive task completion and exercise reversed the detrimental effects of breakfast consumption on RVIP reaction time" would have to be confirmed in a group of habitual "non-breakfast eaters", whose circadian rhythm is adapted to running on stored fuel in the morning, before we ascribe general validity to it.



Potassium Citrate: Could the "Best Calcium Supplement" Contain No Calcium, At All? Usually the reason doctors will prescribe or tell people to take calcium supplements is that they are afraid their patients would otherwise pee out their bones - literally! Unfortunately, that does not reduce but will often rather exasperate the urinary excretion of calcium and thus belongs to the realms of counterproductive or at least incomplete text-book knowledge, which stands in contrast to a handful of studies of which the average physician usually has not heard, before (Harrington. 2003; Karp. 2009; Marangella. 2004, Sakhaee 2005; Taylor. 2010).

Figure 2: Changes in urinary calcium and calcium balance (mg/day), as well as serum parathyroid levels (PHT in pg/dl) after 6 months on 650mg calcium citrate (placebo) with or without 60 or 90mmol potassium citrate
The latter probably won't change with the soon-to-be-published paper that deals with the effects of potassium citrate supplementation on calcium balance in older men and women. And that despite the fact that the results could be of relevance for anyone following a high protein, high fat or SAD diet, as well - especially if he is like Adelfo's client Mr. C and "does not like his vegetables" ;-) After all, the main mechanism by which the administration of 60 or 90 mmol of potassium citrate improved the calcium balance of the subjects who had a low baseline calcium intake and a high phosporus load (556/1338 in the female and 618 / 1410 in the male subject) and a potassium intake 10-15% below the RDA of 3,500mg was the "complete neutraliz[ation]" of the dietary acid load, which can be a serious problem with far-reaching metabolic ramifications not just for the elderly (Mosele. 2012).

In the study at hand, the alkalizing effect of the potassium supplement went hand in hand with increases in urinary potassium (42.0 in the low and  67.3 mmol/day in the high dose arm) and profound decreases in urinary calcium loss. In conjunction with the elevated calcium intake from 630mg of supplemental calcium citrate, all subjects (placebo included) received, this induced a shift from a negative into a positive calcium balance and corresponding decreases in PTH, the hormone that will not just leach calcium out of the bones to keep your serum calcium levels steady (see figure 2), but has also been found to be associated with increased body fat levels (interestingly specifically fat and not other anthropometric markers like body weight!) and metabolic syndrome (Snider. 2005; Hjelmesaeth. 2009)

Is the dosage used in the study already dangerously high? No. 90mmol K-citrate are usually tolerated without problems (this assumes that you have healthy kidneys!), but must be spread across the day and are best ingested with food.
In view of what you've learned about the role of phosphorus in calcium and vitamin D metabolism ("Phosphor, Calcium and Vitamin D"), as well as the potential pitfalls of becoming overtly acidic (scroll down to figure 3) and what you can do to stay on the alkaline side of things, it is probably not necessary I remind you of the fact that you can avoid running into problems in the first place by simply eating a balanced whole foods diet without tons of grainy junk (whole or not) and convenience "foods". If you do that, the use of supplements should be unnecessary and could, if consumed in excess, have serious side effects, which range from gastrointestinal distress over low blood pressure, muscular warkness and dehydration (due to a low sodium : potassium ratio), up to cardiac arrhythmias and - in the worst case - sudden cardiac arrest.



25mg Clomiphene Citrate Still a Good Choice For Non Testosterone Based TRT (or Restart) ... and as if that was not already enough, it will also maintain your bone health, when your testosterone can't do the job for you, or help you and your significant other if you have problems conceiving (see box "Clomiphene citrate?", below; Da Ros. 2012)

Clomiphene citrate? For those of you who have no idea, what clomiphene citrate aka "clomid" is: It's a SERM = selective estrogen receptor modulator - basically a molecule that looks and behaves similar to estrogen, but has only insignificant estrogenic effects, when it binds to the estrogen receptor. Originally developed for the treatment of breast cancer, SERMs have caught some attention within the bodybuilding community as the goto drug to "restart" the HPTA after the use of androgens. This works simply because estrogen, the last hormone in the steroid cascade has the most pronounced suppressive effect on steroid production. As soon as the respective receptors in the brain are blocked and the brain tricked to believe that there is almost no estrogen floating around it will ramp up the hormonal production again and the sex hormone levels will rise. Obviously, this does not work for former performance enhancing drug users, only, but also for men in whom the HPTA or testosterone production is suppressed for other reasons. And as if that was not astonishing enough, clomid has also been used with some success as a fertility drug for women (Zadehmodares. 2012).
In a prospective study the results of which have been published in the International Brazilian Journal of Urology Carlos Teodósio Da Ros and Márcio Augosto Averbeck were able to show that the (in bodybuilding circles probably laughed at) dosage of 25mg/day clomiphene citrate increased the testosterone levels of 125 men with hypogonadism and low libido (mean age was 62 years) from Serum T levels ranged from 309 ng/dL at baseline to 642 ng/dL within no more than 3 months.

What about the side effects? Well, the only ones the scientists observed were improvements in the
post-treatment Quality of Life (QoL) scores
. Total cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose and prolactin did, if anything, improve (!) - statistically significant was yet only the -5% reduction in total cholesterol.

No serious adverse events were recorded. And if it were not for the absence of statistically significant improvements in sexual performance in the 26 men who had already passed the 71y age mark - you could probably say: "It worked like a charm" ;-)



Curried Carrot Soup w/ coconut oil (DrAxe.com) - I doubt the chef who came up with this recipe was aware of a recent study by Conlon et al. which showed that coconut oil can increase carotenoid accumulation in tissue & serum of gerbils by up to 900%(!) over safflower control
Virgin Coconut Oil For Everything - Including Bone Strength! Sounds hilarious, but is true: Researchers from the Pharmacology Department at the Faculty of Medicine of the Universiti Kebangsaan Malaysia in Lumpur, Malaysia, have found that the addition of 8g /100g virgin coconut oil (VCO) to the diets of the ovariectomized rats (this is the standard rodent model of menopause), was more effective than calcium supplements in preventing the menopausal bone loss.

While calcium only prevented the reduction in trabecular separation but failed to increase the bone volume and trabecular number, the rodents in the VCO group had a significantly greater bone volume and trabecular number than the ovariectomized non-supplemented controls, as well.

The scientists speculate that the beneficial effects the coconut oil had on the bone-structure of the estrogen deficient rodents was most likely due its high amount of saturated fats, particularly the medium chain triglycerides (MCTs). At least in my humble opinion the the additional biologically active components like vitamins and polyphenols, probably played an almost as important role. At least, that's what their antiallergenic, antiatherogenic, anti-inflammatory, antimicrobial, antithrombotic, cardioprotective, and vasodilatory effects would suggest - I mean, why don't we simply add antiosteoperotic to that list ;-)

Hungry for more news? Visit the SuppVersity on Facebook!
That's it for today, but there will be more in the days to come... more short news and an article I have promised to write looooong ago. So stay tuned and don't forget to check out the SuppVersity Facebook page for a couple of even shorter news-items on the bone-obesity connection, the potential downsides to chronic high dose glutamine supplementation, why total LDL cholesterol number and even LDL particle size could be less important than we have thought and much, much more ;-)

References:
  • Choi KM, Lee YS, Shin DM, Lee S, Yoo KS, Lee MK, Lee JH, Kim SY, Lee YM, Hong JT, Yun YP, Yoo HS. Green tomato extract attenuates high-fat-diet-induced obesity through activation of the AMPK pathway in C57BL/6 mice. J Nutr Biochem. 2012 Sep 10. pii: S0955-2863(12)00184-2.
  • Conlon LE, King RD, Moran NE, Erdman JW Jr. Coconut Oil Enhances Tomato Carotenoid Tissue Accumulation Compared to Safflower Oil in the Mongolian Gerbil ( Meriones unguiculatus ). J Agric Food Chem. 2012 Aug 16.
  • Da Ros CT, Averbeck MA. Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study. Int Braz J Urol. 2012 Jul;38(4):512-8.
  • Harrington M, Cashman KD. High salt intake appears to increase bone resorption in postmenopausal women but high potassium intake ameliorates this adverse effect. Nutr Rev. 2003 May;61(5 Pt 1):179-83. 
  • Hayatullina Z, Muhammad N, Mohamed N, Soelaiman IN. Virgin Coconut Oil Supplementation Prevents Bone Loss in Osteoporosis Rat Model. Evidence-Based Complementary and Alternative Medicine. 2012; 237236: 8 pages.
  • Hjelmesaeth J, Hofsø D, Aasheim ET, Jenssen T, Moan J, Hager H, Røislien J, Bollerslev J. Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Cardiovasc Diabetol. 2009 Feb 3;8:7.
  • Karp HJ, Ketola ME, Lamberg-Allardt CJ. Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women. Br J Nutr. 2009 Nov;102(9):1341-7. 
  • Marangella M, Di Stefano M, Casalis S, Berutti S, D'Amelio P, Isaia GC. Effects of potassium citrate supplementation on bone metabolism. Calcif Tissue Int. 2004 Apr;74(4):330-5.
  • Moseley K, Weaver C, Appel L, Sebastian A, Sellmeyer DE. Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women. J Bone Miner Res. 2012 Sep 18.
  • Sakhaee K, Maalouf NM, Abrams SA, Pak CY. Effects of potassium alkali and calcium supplementation on bone turnover in postmenopausal women. J Clin Endocrinol Metab. 2005 Jun;90(6):3528-33. 
  • Séralini GE, Clair E, Mesnage R, Gress S, Defarge N, Malatestab M, Hennequin D, de Vendômois JS. Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food and Chemical Toxicology. 2012. Ahead of print.
  • Snijder MB, van Dam RM, Visser M, Deeg DJ, Dekker JM, Bouter LM, Seidell JC, Lips P. Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women. J Clin Endocrinol Metab. 2005 Jul;90(7):4119-23.
  • Taylor EN, Stampfer MJ, Mount DB, Curhan GC. DASH-style diet and 24-hour urine composition. Clin J Am Soc Nephrol. 2010 Dec;5(12):2315-22. 
  • Veaseay RC, Gonazalez JT, Kennedy DO, Haskell CF, Stevenson CS. Breakfast consumption and exercise interact to affect appetite, cognitive performance and mood later in the day. Appetite 59 (2012) 618–638.
  • Wesnes KA, Pincock C, Scholey A. Breakfast is associated with enhanced cognitive function in schoolchildren. An internet based study. Appetite. 2012 Aug 15;59(3):646-649.
  • Zadehmodares S, Niyakan M, Sharafy SA, Yazdi MH, Jahed F. Comparison of treatment outcomes of infertile women by clomiphene citrate and letrozole with gonadotropins underwent intrauterine insemination. Acta Med Iran. 2012;50(1):18-20.

Friday, May 18, 2012

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!