How to Switch Off Your Menstrual Cycle W/ Exercise & Dieting - More Than 22% Deficit ➯ Increased Risk of Menstrual Irregularities + Reduced (!) Weight Loss

Messing with your hormones won't help to reveal your abs, ladies!

I have written about this problem previously. Actually the whole SuppVersity "Athlete's Triad"-Series (read it) is remotely related to it: Women working out like hulk and eating like a sparrow. A behavior that leads to hormonal imbalances and amenorrhea very reliably.

So if you are wondering, why your menstrual cycle is messed up. Why you cannot get pregnant or why you simply stopped menstruating, ladies, this article is for you.

Needless to say that the same goes for male and female trainers, obviously, for whom the results of a very recent study from the Pennsylvania State University and the Penn State University College of Medicine (Williams. 2014).

Low T3 syndrome is also a result of dieting and a part of the (Female) Athletes Triad.

Female Athletes' Body Comp Suf- fers From Dieting

Female Athlete's Triad is not ex- clusively female

Female Athlete's Triad - A Vicious Cycle

Female Athlete's Triad - Recovery Part 1/3

Female Athlete's Triad - Recovery Part 2/3

Female Athlete's Triad - Recovery Part 3/3

The study Nancy I. Williams and her colleagues conducted was designed to confirm or refute the that there would be a dose-response relationship between the induction of menstrual disturbances (luteal phase defects, anovulation, and oligomenorrhea) and the magnitude of energy deficiency.

In other words, the researchers expected that higher energy deficits would incur a significantly greater incidence and more severe disturbances of their menstrual cycle disturbances. To evaluate their hypothesis, the researchers conducted a randomized prospective design that employed controlled feeding and supervised laboratory-based exercise over the course of three menstrual cycles in young, untrained, premenopausal, eumenorrheic women.

Table 1: Overview of the experimental procedures; MC=Menstrual Calendar | Note: Mid-study Body composition testing occurred during Intervention Cycle 2 for most subjects, but in some it occurred during Intervention Cycle 3 (Williams. 2014)

"The study was conducted over three years, with yearly cohorts recruited in the fall of the academic year and followed until the end of spring semester. The controlled feeding and exercise training began after the Screening and Baseline periods, each period lasting one menstrual cycle. All phases of the intervention were anchored to subjects’ menstrual cycles, and each study phase consisted of one menstrual cycle (Intervention Cycle 1, Intervention Cycle 2, Intervention Cycle 3). A post study period of one week where diet and exercise remained controlled allowed for post intervention measurements. The study design is illustrated in Table 1.

Group assignments were based on varying levels of energy deficiency created through a combination of caloric restriction and exercise such that one group remained in energy balance and four groups were in different degrees of an energy deficit. Repeated assessments of menstrual status, metabolic status, and body composition were conducted." (Williams. 2014)

The study was conducted with healthy young, weights-stable women, who had not evidence or history of disordered eating were aged 18 – 30 years, weighed 45 – 75kg and had a normal body fat level of 15 – 35%. The women didn't smoke, were not hormones or anti-contraceptives.

So what did the scientists do?

During the Baseline period, subjects were randomly assigned to an experimental group for the Intervention Cycles 1, 2, and 3 of the study. The goal of the subject groupings was to test the impact of varying levels of an energy deficit created by the combination of caloric restriction and exercise on menstrual function.

Most women ignore the risk of bone loss and only few know that the un- wanted "clinical sequelae", i.e. the nasty pathological consequences, of not eating enough and working out like a maniac include sign. increases in cardiovascular risk (O'Donnell. 2004)

The overlooked significance of hormonal imbalances: As Williams et al. point out, "[a] large body of evidence in a variety of mammalian species has demonstrated a causal link between chronic energy deficiency and the suppression of reproductive function involving the central inhibition of gonadotropin releasing hormone (GnRH) pulsatility" (Williams. 2014). In humans, long term energy deficiency can result in functional hypothalamic amenorrhea, (FHA) and therefore, decrease estrogen exposure, diminishing estrogen’s impact on bone, reproductive, and cardiovascular regulation, often resulting in bone loss (Rencken. 1996; Wade. 1996), stress fractures - specifically in athletes (Barrow. 1988; Bennel. 1999; Brukner. 1997), transient infertility, dyslipidemia, and impaired endothelial function (Friday. 1993, Hoch. 2007; O’Donnell. 2004).

Table 2: Baseline demographic characteristics of study subjects categorized by group (top) and energy balance parameters averaged across Intervention Cycles 1-3 for each group (bottom) - directly from Williams (2014)

They were assigned to either a control group that did not exercise and consumed an amount of calories estimated to maintain body weight, a control group that exercised, but received extra food calories to remain in energy balance (exercising controls or EXCON), or one of four groups that exercised and were prescribed reduced energy intake to create varying levels of an energy deficit (energy deficit or ED groups). ED groups were defined by an energy prescription comprised from the quantity of calories provided as food and the quantity of calories expended as exercise. ED groups were prescribed targeted reductions in energy intake (7 days/week) compared to their Baseline energy needs ranging from – 15% to – 30% in combination with prescribed increases in exercise energy expenditure (5 days/week) equivalent in calories to + 15% to + 30% of Baseline energy needs.

Starvation diets will also mess w/ your thyroid | learn more

So, how low can you go? The scientists fount that the estimates of the magnitude of energy deficiency associated with menstrual disturbances ranged from -22% (ED2) to -42% (ED3), reflecting an energy deficit of -470 to -810 kcal per day, respectively. In contrast to the what Williams et al. expected, the severity of menstrual disturbances, was not dependent on the magnitude of energy deficiency and is thus not a gauge to estimate how much more you'd have to eat to become fully functional again.

As the researchers point out, specifically, the initial four energy deficit groups were intended to represent 1) an increase of 15% kcals of exercise (15% deficit), 2) an increase of 30% kcals of exercise (30% deficit), 3) a decrease of 15% in dietary intake, combined with an increase of 15% of exercise, (30% deficit) and 4) a decrease of 30% in dietary intake, combined with an increase of 30% kcals of exercise (60% deficit).

Figure 1: Daily energy deficit (left) and corresponding menstrual irregularities (right) the Pennsylvanian researchers observed during the intervention (Williams. 2014)

As you can see in Figure 1 the plan worked out quite well and the original hypothesis that the severity of the energy deficit would correlate with the risk of overall risk of menstural irregularities. What is interesting, though, is that the overall linear increase was visible mostly for the luteal phase disturbances. Actual unovulatory cycles were observed only in groups ED2 & ED3, but - and this is important - for some women, it was enough to just work out to induce oligomenorrhic cycles, i.e. infrequent (or, in occasional usage, very light) menstruation.


Next to the menstrual irregularities, which were obviously what the scientists were actually interested in, the scientists also observed that the 34 subjects lost weight, 3.8 kg in the ED1 and - listen up ladies! - only 2.8 kg and 2.6 kg in the high(er) energy deficit groups ED2 and ED3 (no significant weight loss occurred in the exercise only, i.e. the EXCON group).

Figure 2: Amount of weight (in kg) the women in the four groups lost over the course of the complete study period (Williams. 2014)

Bottom line: Let me say this right away. It's not unfair, but very clever that nature made sure that starving women cannot become pregnant.

If you look at the "target outcome" of most women's dietary interventions, i.e. the amount of weight they lose (see Figure 2), you will also have to concede that what many women believe would be "unfair" actually protects them from ineffective starvation diets. It was after all not the group with the highest, but the group with the lowest energy deficit that lost the most weight. So, ladies, be sure to remember this and if you are still not convinced that starving yourself is not the magical weight loss solution that will give you the "shape cover model" body you're looking for, take another look at the "9 Rules of Sensible & Effective Dieting" | Comment on Facebook.

References:

• Barrow, Gray W., and Subrata Saha. "Menstrual irregularity and stress fractures in collegiate female distance runners." The American journal of sports medicine 16.3 (1988): 209-216.
• Bennell, Kim, et al. "Risk factors for stress fractures." Sports Medicine 28.2 (1999): 91-122.
• Brukner, Peter, and Kim Bennell. "Stress fractures in female athletes." Sports Medicine 24.6 (1997): 419-429.
• Friday, Karen E., et al. "Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol levels in amenorrheic athletes: effects of endogenous hormone status and nutrient intake." The Journal of Clinical Endocrinology & Metabolism 77.6 (1993): 1605-1609.
• Hoch, Anne Z., et al. "Athletic amenorrhea and endothelial dysfunction." Wisconsin Medical Journal 106.2 (2007).
• O’Donnell, Emma, and Mary Jane De Souza. "The Cardiovascular Effects of Chronic Hypoestrogenism in Amenorrhoeic Athletes." Sports Medicine 34.9 (2004): 601-627.
• Rencken, Monica L., Charles H. Chesnut, and Barbara L. Drinkwater. "Bone density at multiple skeletal sites in amenorrheic athletes." Jama 276.3 (1996): 238-240.
• Wade, GEORGE N., JILL E. Schneider, and H. Y. Li. "Control of fertility by metabolic cues." American Journal of Physiology-Endocrinology And Metabolism 270.1 (1996): E1-E19.
• Williams, Nancy I., et al. "Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction." American Journal of Physiology-Endocrinology and Metabolism (2014): ajpendo-00386.

The Female(?) Athlete Triad - Part II/III: LH, GH, IGF1, Insulin, Ghrelin, Leptin & Co Form a Self-Perpetuating Vicious Cycle

I usually rant against pizza and beer, but once the athlete triad has struck, they can be an occasional part of the "healing protocol".

In last Sunday's first installment of this series we have taken a look at the prevalence, etiology and fundamental cause of an entity that is, and I am repeating myself here, profoundly mislabeled as the "female athlete triad". In fact, it is, as we have learned in the last installment, neither an exclusively female thing, nor a triad. If anything, it is a quintet or sextet. To make that clear, and give you guys, who make the same mistakes, but usually with less detrimental consequences, I will once more refer to it as "athlete triad" = AT,  in this second part of the Female(?) Athlete Triad Series in which we will take a look at the endocrine underpinnings of the previously described consequences of the temporary and long-term energy deficiency we have identified as the single most important causative factor of the onset of the "triad" last Sunday.

Which endocrine factors are figuring, here?

Instead of overwhelming you with the details right from the start, I decided to compile a list based on a cross-section of the dozens of articles I have read in the course of my eventually futile quest for a single definitive answer to the question, "Which hormonal or metabolic consequence of restrictive eating and excessive training is to blame for the fatigue, the low sex hormones concentration,the  bone resorption, the anemia, the absence of menses / lack of libido, the performance decreases and the whole string of pathological features, we have explored in the last installment?"

"Refeeding is not an option, because you will only become fat!" FALSE! Yet another myth without substantial scientific foundation that probably arises from the disturbed self-perception of those affected by AT and AN. In fact, the fat stores are the last thing that will be restored (Golden. 2004). This is probably also one of the reasons why "refeeding" often does not appear to work, because the basal energy requirements will increase with every pound of lean tissue you add back to your frame, so that athletes suffering from the "triad" will have to continuously increase their energy consumption. Unfortunately, most athletes will fail to do the former (also because exercise & stress can blunt hunger) and instead react with an increase in workout intensity, now that they are finally able to work out, again. This, in turn, will restore or even exacerbate the energy deficit and thus worsen not improve their physiological problems, even if their scale shows that they have already gained 5-10kg. If you take a look at figure 1 you will also realize that, at least in women, a baseline level of total (not relative!) body fat appears to be necessary to maintain regular menses (in men to maintain normal total testosterone & SHBG, but not so much free testosterone levels or reproductive function).

• low luteinizing levels are unquestionably among the elemental features and causally responsible for the occurance of menstrual disorders / lack of libido and the correspondingly low estrogen and testosterone levels in women and men
• TSH levels are not a valid / reliable indicator for the presence of absence of AT, because they can be both slightly increased or normal in the presence of low T4 and low T3 levels, as  - and this is far more often the case - TSH can be low despite low free thyroid hormone levels (usually in the presence of a low T3/rt3 ratio; if anything this would be a good indicator of beginning or full-blown AT)
• the circadian cortisol rhythm is whacked in men and women, alike; characteristic are the absence of an appropriate cortisol spike in the morning as well as the normal decline in cortisol levels  in the course of the day; metaphorically speaking, as the athletes triad progresses, the "mountain range" turns into mesa and eventually into a plane lowland
• the quartet of (mostly) sub-clinical hypogylcemia, low insulin, extreme high / or totally blunted insulin sensitivity, low IGF-1 and high catecholamine levels cannot be seen in isolation, most detrimental are yet probably the first and last of these four glucose-related players in the AT concert, as the former entails the constant risk to run out of "brain fuel" (in the absence of alternative fuel sources) and can - in the absence of adequate corticosteroid expression - become potentially life-threatening and the latter, i.e. low IGF-1 levels and very low IGF-1 to IGF1 binding protein 4 being one of the, if not the central factor involved in the the long-term physical decline of muscle, bone, organ and even brain mass.

As I have repeatedly emphasized in the last installment, the underlying cause, the trigger, maintaining factor and thus most important setscrew of the athlete triad (female or male) is an over-exaggerated and / or  long-lasting (weeks to months, in the worst case years; see Sundgot-Borgen. 2000) discrepancy between energy intake and expenditure, your body will initially try, but eventually fail to compensate by

• tapping into its energy stores in form of body fat, muscle and organ mass, the insulating fat around nerves and organs, etc.,
• continuously decreasing its metabolic activity (esp. thyroid metabolism),
• shutting down non-vital, but energy-intensive (e.g. immune and reproductive system) bodily functions, to prioritize short term survival of the individual over long-term survival and the conservation of the species

Therefore it is an indispensable and in many cases even sufficient prerequisite to restore an adequate supply of nutrients, and abolish temporarily better reverse the discrepancy between "energy in" and  "energy out" (please read the information in the red box next to the list of the previous paragraph, as well).

And what about leptin, ghrelin, adiponectin ... ?

Figure 1: In female athletes, only total fat mass, not body fat % or BMI are associated w/ AT (here identified by amenorrhea; top, left); the correspondingly low pulsatile (not baseline, see lower left) of LH correlate negatively with ghrelin and positively with leptin (top, right); while LH and leptin show a lack of pulsality, the ghrelin levels are not simply elevated, they also have a higher pulse size, amplitude and total polsatile secretion compared to control and eumenorrhetic athletes (bottom; LH, ghrelin, leptin expressed relative to non-athletic control; based on Ackerman. 2012)

Similar to the facilitative effects of the "hunger high", the "evolutionary advantage" that's turning its ugly face on everyone, who's willing to dig a deep enough whole (see Part I), the endocrine imbalances, as well as the reduced leptin) or over-pronounced (adiponectin) release of adipokines and the disturbances of the glucose, fatty acid and cholesterol metabolism start to take on a life of their own.

And as if that alone would not already make it difficult enough to separate cause and effect, it does actually appear likely that the order may even be reversed over time - not unlike the chicken that will hatch and eventually lay an egg. 

As discussed in the last installment, the combination of over-exercising and fasting, which may at time-point T0 actually have been the root cause of the problem will often turn into a strategy to stave off the impeding total breakdown. It becomes sort of a conditioned response to the constant starvation, which  will then no longer manifest itself in the form of hunger, but as anxiety and an almost compulsive urge to exercise (this is particularly well-established for anorexics; Teufel. 2008). And while the latter can be motivated by the desire to increase athletic performance and/or lose even more body fat, it does have a very real, often under-appreciated, physiological underpinning.

If you like, you could argue that the urge of the starved athlete to exercise is yet another "evolutionary conserved" automatism that mirrors the well-known food-seeking behavior rodents display  in periods of food deprivation and in response to the stimulatory effects of ghrelin on the orexin neurons in the brain (Yamanaka. 2003).

From ghrelin to growth hormone to IGF-1 and back

At the same time, the combination of exercise, low triglyceride, low free fatty acid and exuberant levels of the "hunger hormone" ghrelin leads to an overexpression of growth hormone (Scacci. 2003), subsequent increases in adiponectin (Wölfing. 2008), which will in turn decrease progesterone and androstenedione production and LH receptor expression in ovarian cells (Lagaly. 2008) and GnRH and LH release in the pituitary (Rodriguez-Pacheco. 2007; Lu. 2008). The surprisingly high adiponectin levels (surprisingly in view of the often dangerously low levels of adipokine producing body fat) will further increase the borderline pathological insulin sensitivity and thus lower the already rock bottom blood glucose and basal, as well as (post-)prandial insulin levels even further.

Figure 2: Illustration of the self-perpetuating vicious cycle of the athlete's triad (AT)

With their suppressive effect on leptin (Böni-Schnetzler. 1999), the high growth hormone levels and low body fat reserves are probably the most important contributers to the pathologically low, in fact quasi non-existent basal leptin secretion (see figure 1). And the low insulin levels don't just compromise the normal food-induced prandial suppression of ghrelin (Murdolo. 2003), they also hamper the production of IGF-1 (especially in the liver), so that athletes who suffer from the "triad" cannot derive any anabolic benefits from their high growth hormone levels, since the latter are largely mediated by the stimulatory effect of growth hormone on the production of IGF-1... what you are seeing here is thus a self-perpetuating vicious circle, you can extricate yourself from only by a multi-faceted approach the pillars of which are an..

* in view of the insulinogenic effects of whey and the pro-IGF-1 effects of casein (Hoppe. 2009), and the anti-catabolic effects of CLA & omega-3 you should - if by any means possible - incorporate dairy products from preferably grass fed dairy (butter, milk, cheese, yoghurt, quark / curd cheese, fermented dairy and if you want protein powders) in your diet regularly, better daily.

1. adequate and continuous energy supply to control ghrelin levels and help stabilize blood sugar (and thus glucocorticoid) levels and restore normal leptin and adiponectin expression,
2. increased low GI (to avoid reactive hypoglycemia) carbohydrate and protein intakes to normalize glucose levels, suppress ghrelin, increase insulin and IGF-1 levels* (Foster-Schubert. 2008; suggested read: "Carbohydrate Shortage in Paleo Land"),
3. balanced intakes of all types of natural fats, with an emphasis on long-chain PUFAs from food including a reasonable amount of "bad" omega-6 fatty acids and w/out fish oil or other omega-3 supplements, which would further blunt the already compromised glucocorticoid response and the leptin secretion (Kratz. 2002; suggested read "Omega-3 and Low Cortisol"), and
4. profound reductions in training volume to lower GH, cortisol, catecholamin and energy requirements and a (temporary) reorientation towards low volume strength training that will help increase bone density and IGF-1 expression (Davee. 1990)

Now, this may sound hilarious, but for the time being, laziness, pizza and beer - in moderation - are actually your friends. In that, I am not suggesting that you have to copy the patient, Chris Kresser mentioned several times on the old "Healthy Skeptic" podcasts (now RHR) about a client, who "cured" his longstanding physiological, and as I suspect psychological problems with pizza and beer, but the third pillar of this guy's regimen is actually a must: Go out with friends and start to enjoy your life again! Without thinking about food and exercise and sticking to whatever form of restrictive "diet" all the time.

Figure 3: Development of BMI (blue), leptin (red), adiponectin (green) levels in 8 female adolescent malnourished AN patients (based on Modan-Moses. 2007)

Apropos, third pillar. I have already had my short intense workout for the day, I have eaten well, but I have not hung out with friends. In other words, I will postpone the in-depth discussion of the energy and nutrient requirements, useful and detrimental supplements and medications, as well as necessary and facilitative tweaks to your workout routine to the next week, add another Roman "I" to the second "II" in "Part II/II" in the preliminary headline of this post and leave you (hopefully not too frustrated) with the graphical illustration of the effects re-feeding, alone, and a normalization of the body weight from a BMI of 16kg/m² to ~19kg/m² can have on the skewed basal leptin and adiponectin in figure 3.

In view of the fact that other studies have shown that this increase in weight, which must not be confused with a mere increase in adiposity, i.e. body fat percentage (go back to figure 1 if you already forgot that the absolute not the relative fat mass counts and please remember that the latter includes the fat in the myelin sheaths of your nerves, the protective fat around the organs, the fat in your brain etc.), does help with the normalization of both insulin and ghrelin (Otto. 2001), growth hormone and IGF-1 (Argente. 1997) and is in some cases even sufficient to restore most of the endocrine abnormalities (Scheid. 2010), many of the lessons we will learn in the next (and according to my current plans last ;-) installment can also be applied to a lean bulk - and that goes irrespective of your gender and your whether or not you have already fallen victim to the athlete triad!

References

• Ackerman KE, Slusarz K, Guereca G, Pierce L, Slattery M, Mendes N, Herzog DB, Misra M. Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls. Am J Physiol Endocrinol Metab. 2012 Apr 1;302(7):E800-6.
• Argente J, Caballo N, Barrios V, Muñoz MT, Pozo J, Chowen JA, Morandé G, Hernández M. Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation. J Clin Endocrinol Metab. 1997 Jul;82(7):2084-92.
• Beals KA, Manore MM. Disorders of the female athlete triad among collegiate athletes. Int J Sport Nutr Exerc Metab. 2002 Sep;12(3):281-93. 
• Boag F, Weerakoon J, Ginsburg J, Havard CW, Dandona P. Diminished creatinine clearance in anorexia nervosa: reversal with weight gain. J Clin Pathol. 1985 Jan;38(1):60-3. 
• Böni-Schnetzler M, Hauri C, Zapf J. Leptin is suppressed during infusion of recombinant human insulin-like growth factor I (rhIGF I) in normal rats. Diabetologia. 1999 Feb;42(2):160-6.
• Caspar-Bauguil S, Montastier E, Galinon F, Frisch-Benarous D, Salvayre R, Ritz P. Anorexia nervosa patients display a deficit in membrane long chain poly-unsaturated fatty acids. Clin Nutr. 2012 Jun;31(3):386-90.
• Davee AM, Rosen CJ, Adler RA. Exercise patterns and trabecular bone density in college women. J Bone Miner Res. 1990 Mar;5(3):245-50.
• Di Carlo C, Palomba S, De Fazio M, Gianturco M, Armellino M, Nappi C. Hypogonadotropic hypogonadism in obese women after biliopancreatic diversion. Fertil Steril. 1999 Nov;72(5):905-9.
• Di Luigi L. Does the high performance athlete need hormone replacement? Endocrine Abstracts. 2012; 29: 35.1 
• Foster-Schubert KE, Overduin J, Prudom CE, Liu J, Callahan HS, Gaylinn BD, Thorner MO, Cummings DE. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J Clin Endocrinol Metab. 2008 May;93(5):1971-9.
• Figueiro MG, Plitnick B, Rea MS. Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults. International Journal of Endocrinology. 2012, Article ID 530726.
• Golden NH, Meyer W. Nutritional rehabilitation of anorexia nervosa. Goals and dangers. Int J Adolesc Med Health. 2004 Apr-Jun;16(2):131-44.
• Hernández M, Argente J, Navarro A, Caballo N, Barrios V, Hervás F, Polanco I. Growth in malnutrition related to gastrointestinal diseases: coeliac disease. Horm Res. 1992;38 Suppl 1:79-84.
• Hobart J, Smucker D. The Female Athlete Triad. Fam Physician 2000; 61:3357-64,3367. 
• Hoppe C, Mølgaard C, Dalum C, Vaag A, Michaelsen KF. Differential effects of casein versus whey on fasting plasma levels of insulin, IGF-1 and IGF-1/IGFBP-3: results from a randomized 7-day supplementation study in prepubertal boys. Eur J Clin Nutr. 2009 Sep;63(9):1076-83.
• Khan KM, Liu-Ambrose T, Sran MM, Ashe MC, Donaldson MG, Wark JD. New criteria for female athlete triad syndrome? As osteoporosis is rare, should osteopenia be among the criteria for defining the female athlete triad syndrome? Br J Sports Med. 2002 Feb;36(1):10-3. 
• Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007 Jan;8(1):21-34.
• Kratz M, von Eckardstein A, Fobker M, Buyken A, Posny N, Schulte H, Assmann G, Wahrburg U. The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women. J Clin Endocrinol Metab. 2002 Nov;87(11):5008-14.
• Lagaly DV, Aad PY, Grado-Ahuir JA, Hulsey LB, Spicer LJ. Role of adiponectin in regulating ovarian theca and granulosa cell function. Mol Cell Endocrinol. 2008 Mar 12;284(1-2):38-45.
• Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. Erratum in: N Engl J Med 1995 Aug 10;333(6):399.
• Loucks AB, Verdun M, Heath EM. Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J Appl Physiol. 1998 Jan;84(1):37-46.
• Loucks AB. Energy availability, not body fatness, regulates reproductive function in women. Exerc Sport Sci Rev. 2003 Jul;31(3):144-8.
• Lu M, Tang Q, Olefsky JM, Mellon PL, Webster NJ. Adiponectin activates adenosine monophosphate-activated protein kinase and decreases luteinizing hormone secretion in LbetaT2 gonadotropes. Mol Endocrinol. 2008 Mar;22(3):760-71. Epub 2007 Nov 15.
• Manore MM. Dietary recommendations and athletic menstrual dysfunction. Sports Med. 2002;32(14):887-901. 
• Mikos AE, McDowell BD, Moser DJ, Bayless JD, Bowers WA, Andersen AE, Paulsen JS. Stability of neuropsychological performance in anorexia nervosa. Ann Clin Psychiatry. 2008 Jan-Mar;20(1):9-13.
• Miller SM, Kukuljan S, Turner AI, van der Pligt P, Ducher G. Energy deficiency, menstrual disturbances, and low bone mass: what do exercising Australian women know about the female athlete triad? Int J Sport Nutr Exerc Metab. 2012 Apr;22(2):131-8.  
• Modan-Moses D, Stein D, Pariente C, Yaroslavsky A, Ram A, Faigin M, Loewenthal R, Yissachar E, Hemi R, Kanety H. Modulation of adiponectin and leptin during refeeding of female anorexia nervosa patients. J Clin Endocrinol Metab. 2007 May;92(5):1843-7. Epub 2007 Feb 27.
• Mont L, Castro J, Herreros B, Paré C, Azqueta M, Magriña J, Puig J, Toro J, Brugada J. Reversibility of cardiac abnormalities in adolescents with anorexia nervosa after weight recovery. J Am Acad Child Adolesc Psychiatry. 2003 Jul;42(7):808-13.
• Murdolo G, Lucidi P, Di Loreto C, Parlanti N, De Cicco A, Fatone C, Fanelli CG, Bolli GB, Santeusanio F, De Feo P. Insulin is required for prandial ghrelin suppression in humans. Diabetes. 2003 Dec;52(12):2923-7.
• NCAA® Sports Sponsorship and Participation Rates Report • 1981-82 – 2010-11.  
• Orlandi E, Boselli P, Covezzi R, Bonaccorsi G, Guaraldi GP. Reversal of bone marrow hypoplasia in anorexia nervosa: case report. Int J Eat Disord. 2000 May;27(4):480-2.
• Ott V, Fasshauer M, Dalski A, Meier B, Perwitz N, Klein HH, Tschöp M, Klein J. Direct peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res. 2002 Nov-Dec;34(11-12):640-5.
• Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, Heiman ML, Lehnert P, Fichter M, Tschöp M. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol. 2001 Nov;145(5):669-73.
• Rguibi M, Belahsen R. Body size preferences and sociocultural influences on attitudes towards obesity among Moroccan Sahraoui women. Body Image. 2006 Dec;3(4):395-400. Epub 2006 Sep 7.
• Rodriguez-Pacheco F, Martinez-Fuentes AJ, Tovar S, Pinilla L, Tena-Sempere M, Dieguez C, Castaño JP, Malagon MM. Regulation of pituitary cell function by adiponectin. Endocrinology. 2007 Jan;148(1):401-10.
• Scacchi M, Ida Pincelli A, Cavagnini F. Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa. Front Neuroendocrinol. 2003 Jul;24(3):200-24.
• Scheid JL, De Souza MJ. Menstrual irregularities and energy deficiency in physically active women: the role of ghrelin, PYY and adipocytokines. Med Sport Sci. 2010;55:82-102.
• Schtscherbyna A, Barreto T, de Oliveira FP; Luiz RR, de Abreu Soares RR, Gonçalves Ribeiro B. Age of onset training but not body composition is crucial in menstrual dysfunction in adolescent competitive swimmers. Rev Bras Med Esport. May/June 2012; 18(3).
• Steinberg SE, Nasraway S, Peterson L. Reversal of severe serous atrophy of the bone marrow in anorexia nervosa. JPEN J Parenter Enteral Nutr. 1987 Jul-Aug;11(4):422-3.
• Skarda ST, Burge MR. Prospective evaluation of risk factors for exercise-induced hypogonadism in male runners. West J Med. 1998 Jul;169(1):9-12.
• Sundgot-Borgen J. [Physical activity and reproductive health]. Tidsskr Nor Laegeforen. 2000 Nov 20;120(28):3447-51.
• Teufel M, Zipfel S, Herpertz S, Zwaan M. (ed.). Handbuch Essstörungen und Adipositas. Springer Berlin Heidelberg. 2008. 
• Williams NI, Helmreich DL, Parfitt DB, Caston-Balderrama A, Cameron JL. Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training. J Clin Endocrinol Metab. 2001 Nov;86(11):5184-93.
• Wölfing B, Neumeier M, Buechler C, Aslanidis C, Schölmerich J, Schäffler A. Interfering effects of insulin, growth hormone and glucose on adipokine secretion. Exp Clin Endocrinol Diabetes. 2008 Jan;116(1):47-52.
• Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami K, Sugiyama F, Goto K, Yanagisawa M, Sakurai T. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron. 2003 Jun 5;38(5):701-13.

The Female(?) Athlete Triad - Part I/III: How An Evolutionary Advantage Can Turn Its Ugly Face On Both Sexes!

The cover of the Vogue is usually not the place to turn to, if you are looking for role-models, but let's be honest: Do you believe Hope Solo or Serena Williams suffer from amenorrhea or their fellow Olympian Brian Lochte from low testosterone? I don't think so. So, there must be something "real" athletes do that way too many weekend warriors, who are in it, often to look just like their stars don't do - and in this multi-part SuppVersity Special, we are going to figure out what this may be.

I guess some of you will already have believed that I had forgotten about the requested and promised article on the "Female Athlete Triad". As you can easily see, this is not the case and still, I must admit that it will take another week until I will eventually have make good on my promise, as this is only the first part of a multi-part feature.

The main reason I decided to split things up is that I did not want you to simply skip on the fundamental information you will get today and fast forward to the potential solutions to the problem, I will present in the next installment.

After all, the idea of the SuppVersity is not to present cookie-cutter guru advice that may or may not work for you, but rather to put you into a position, where you do at least understand, at best have the skills to question, modify and tweak any exemplary "plans of attack" I will be outlining in upcoming the second part of this series... and if my past efforts to provide you with a basic understanding of your own metabolism have not totally failed, I would suspect that many of you will be able to come up with their own preliminary conclusions after reading this lengthy, but as I hope informative and not overtly complicated first part of the series.

"Female athlete triad:" How the problems start with a false label, already

But my bones are still strong! Specifically the inclusion of osteoporosis as an obligatory criteria for the diagnosis of the female athlete triad is nonsensical and was repeatedly criticized (e.g. Kahn. 2002), as it excludes a large, if not the major part of women (and men) who suffer from a syndrome the prevalence and consequences of which are thus largely underestimated. Moreover, in weight bearing sports, for example the load alone will counter the occurrence of osteoporosis, while other consequences like musculoskeletal injuries will be more prevalent.

So, let's initially take a look at what we are actually talking about here. The phenomenon itself is often somewhat misleadingly labeled as the "female athlete triad" (FAT; or AT w/out the sex-specificity), a term which falsely implies that it was sex-specific and men were immune to it and, what may be even worse, that it would be quite easy to diagnose as it comprises a "triad" of

• low energy availability / disordered eating
• amenorrhea, and
• osteoporosis

Unfortunately, things are much more complex than that and when an athletes health has been deteriorated so much, already, that amenorrhea (or very low testosterone in men) and osteoporosis are already showing their ugly faces, reversing the low energy availability and / or disordered eating, which usually goes hand in hand with months of overtraining, may be enough to keep the status quo, but won't reverse the amenorrhea and the underyling hormonal imbalance.

How prevalent is this misery?

Even if we don't extend our definition to include overall exhaustion and stagnating performance on the "harmless" and "heart disease" and "sudden cardiac death" on the other "life-threatening" end of the continuum, but simply include low testosterone levels and minor menstrual irregularities into our definition of AT (athlete triad), the answer to the above question is "It is rampant!" So rampant in fact that Luigi Di Florence chose the title "Does the high performance athlete need hormone replacement?" for a talk he held at a recent conference. In the respective abstract (a paper has not yet been published), he states:

Figure 1: Moroccan Sahraoui women still have a very different beauty-ideal than Western women. According to the data Rgubi et al. collected in 2006, their female beauty-ideal is heavier than the "health ideal". There is however a clear trend towards a "westernization" among the younger generation (data based on Rguibi. Now, tell me, where would you place yourself, your beauty-ideal and your health ideal on the graphic in the upper left hand of this figure?

"Exercise per se is associated to the release of different hormones: acute exercise stimulates an acute hormones secretion (e.g. catecholamines, growth hormone, CRH-ACTH-cortisol, testosterone) while chronic exercise (training) is able to modify hormones secretion at rest and their activation during acute exercise. [...] besides symptomatic classical diseases or conditions that may reduce/alter the qualitative/quantitative hormones secretion, serious clinical concerns exist for asymptomatic endocrine hypo-function (e.g. sub-clinical hypogonadism, growth hormone deficit and hypothyroidism), particularly in adult athletes. For example, in master athletes we observed an high prevalence of undiagnosed severe (12%) and mild (18%) hypo-testosteronemia frequently in the absence of clinical symptoms. [...] Unfortunately, few studies evaluated the prevalence of reduced hormones secretion in athletes and the concept of adapted hormone replacement in high competitive athletes." (Di Luigi. 2012; my emphases)

The absence of a clearcut definition of "the female athlete triad", the ignorance towards the existence of corresponding problems in male athletes (of all age groups!) and the vast differences within different study populations makes it very difficult to quantify, how many men and women actually suffer from AT. The little data we have is obviously sex-specific and of rather qualitative nature, as the following citation from Hobart 2000 goes to show you:

Although the exact prevalence of the female athlete triad is unknown, studies have reported disordered eating behavior in 15 to 62 percent of female college athletes. Amenorrhea occurs in 3.4 to 66 percent of female athletes, compared with only 2 to 5 percent of women in the general population. (Hobart. 2000)

If we take the latest NCAA numbers as a baseline (191,131 female athletes in the year 2011) and multiply them by 2x to include those lonesome gymrats and crossfitters out there who are often even more likely to overdo it than their co-ed peers who usually work with a more or less qualified coach, of whom you would expect that he or she is able to call a halt before it is too late, we are talking about ~13,000-252,000 young women and an undisclosed number of young men, here!

"Sh..Sh.. let's not talk about it!"

Pah, that's all not problematic! Really? A 2002 study from the Bell State University found that aside from the menstrual irregularity, which have been reported by 31% of the athletes not using oral contraceptives, both, muscle and bone injuries were rampant: 65.9% and 34.3%, in the aesthetic versus endurance and team/anaerobic sports, respectively. (data based on Beals. 2002)

Against that background it is almost careless, how little this topic is talked about - especially among athletes and fitness junkies! No wonder that only 10% of the 191 female exercisers (age 18-40 yr), engaging in ≥2 hr/wk of strenuous activity, Miller et al. questioned for their 2012 study on "the knowledge, attitudes, and behaviors of regularly exercising adult women in Australia", could name the initially mentioned three components of the female athlete triad:.

"Regardless of reported history of stress fracture, 45% of the respondents did not think that amenorrhea (absence of menses for ≥3 months) could affect bone health, and 22% of those involved in lean-build sports would do nothing if experiencing amenorrhea (vs. 3.2% in non-lean-build sports, p = .005)." (Miller. 2012; my emphases)

This lack of knowledge and - in parts - even downright ignorance towards the problem certainly raises the question:

"How do I actually realize I am about to develop the (female) athlete triad (AT)?"

I guess, we can derive a (not the!) answer to this question if we take a closer look at an overview of the etiology that has been part of a 2002 analysis by Melinda M. Manore from the Department of Nutrition and Food Management at the Oregon State University in Corvallis, Oregon, USA (see figure 2).

Figure 2: Etiology of the (female) athlete syndrome (and related pathologies) and signs you have to observe, in oder not to to realize what you have been doing when the potentially life-threatening long-term conequences, i.e. bone loss, cardiovascular disease and hardly reversible issues with reproductive function are showing (inspired by Manore. 2002)

I pimped the original graphic with a couple of remarks that should make one thing pretty obvious: At the very moment, when the "classic" features become obvious, it's actually already to late. The best you can hope for, when your menses start to disappear is that neither your cognitive abilities, nor your cardiovascular or bone health are not yet compromised, as well.

There is hope - even after the horse has bolted

"Men can't be anorexic?!" False! According to the latest data from the South Carolina Department of Mental Health there are currently 1,000,000 male US citizens suffering from eating disorders. Their estimated stake among anorexics and bulemics is between 10-15%. Among adolescents, anorexia is the 3rd most common chronic illness, and many of it's physical features are identical to those of the "female" athlete triad - not the least due to the fact that excessive exercise is often part of the pathology. The boundaries between them are fluid. The mortality rate associated with anorexia nervosa is 12x higher than the death rate of ALL causes of death: 5 – 10% of anorexics die within 10 years after contracting the disease; 18-20% of anorexics will be dead after 20 years and only 30 – 40% ever fully recover.

The good news is that our bodies (male and female) are self-repairing machines, evolutionary designed to take beating after beating - esp. if those "beatings" resemble periods of famine. From studies in anorexic men(!) and women we know that many of the pathological features of self-cannibalism (this, and nothing else is what your body is doing, when you constantly deprive it of an adequate supply of energy, as it is the case in the accute phases of the athlete triad) are reversible.

Mont et al. who have been following 31 severely underweight anorexic adolescents with body mass indexes of 15.2 +/- 2 kg/m², sinus bradycardia (=abnormally slow heart beat), decreased left ventricular mass, and diminished thickness of cardiac walls in 35%, 93% and 70%, respectively, report for example:

"After refeeding, a significant decrease in QT interval (p <.05) and QT dispersion (p <.01) was observed. Echocardiograms showed an increase in cardiac diameters (p <.01), left ventricular mass (p <.001), and cardiac output (p <.001). There was also an improvement in the exercise capacity (p <.05) and a normalization of the heart rate and heart rate variability (p <.05)." (Mont. 2012)

Allegedly, few athletes will maneuver themselves into a situation, where they are actually so weak that they can barely walk (which is unfortunately the case for way too many young anorexic patients), their susceptibility to sudden cardiac death and other CVD-related diseases is probably even higher, due to the exercise induced chronic overload of their cardiovascular system.

With the athlete's triad an evolutionary advantage is turning is turning against us

Athlete or not, even these severe physical abnormalities usually disappear with adequate rest, lots of patience and, most importantly, a progressive increase in energy intake (the increases in lean mass, i.e. muscle, organ and bone!, wants to be fed and the the metabolic switch from "energy save" to "normal" mode will increase the energetic demands even more). In fact, even in severely anorexic patients, where most of these pathologies are more severe than in athletes, renal abnormalities (Boag. 1985), atrophy of the bone marrow (Steinberg. 1987; Orlandi. 2000), cognitive impairment (Mikos. 2008) and most of the other functions that are related to survival (not reproduction!) usually recover with adequate energy intake, alone.

Without the evolutionary preserved, catecholamine and glucocorticoid driven "hunger high" our ancestors needed to keep going until they finally found something to eat, neither anorexia (AN), nor the athlete triad (AT) would "work".

The fact that many, if not most of the patients feel that the latter would not help and they would "just become fat", has both psychological, as well as physiological roots, which are related to (a) a distorted body image (which has by the way nothing to do with "being crazy", let alone "dumb" or "stupid") and (b) the loss of the "hunger high", which has previously been masking all the ailments and the total exhaustion and will begin to fade after only 1-2 days of sufficient energy supply and rest.

For many, it does in fact feel, as if they had just been hit by a truck, but in fact very truck has rolling right over them for years now and the person behind the steering wheel, was nobody else than the patient him-/herself.

Without the hilarious amounts of glucocorticoids (cortisol) and excitatory neurotransmitters their bodies seize producing, now that they are no longer necessary to keep the brain from dying a hypoglycemic death and the patients able and motivated to "seek for food" (another evolutionary preserved mechanism, by the way), all the weight of years of over-training and under-eating hits them all at once. In conjunction with the unwanted, but inevitable weight gain, of which Golden et al. state that it comes - specifically in this early phase - almost exclusively from increases in body water, organ, bone and muscle mass (Golden. 2004), this often triggers a relapse into the old "cosy" stress pattern of under-eating and over-exercising. And what's really nasty, here, is that this will provide (felt) "relief" within days, if not hours and via the exact same mechanism that has kept the patients going (and later alive!) over the past months and years: HUNGER (not workout) STRESS!

Not BMI, not fat, not exercise, but simply a constant state of energy deprivation is the culprit

Since we are all aware that weight gain does not happen over night, but the aforementioned perceived aggravation of fatigue can, it should be obvious that neither a low body weight, let alone the amount of body fat a person, man or women, is carrying on his/her frame (scientists refer to this as the "body composition hypothesis), nor the exercise induced stress ("stress hypothesis"), of which I have just outlined that it is a necessary and life-saving reaction to starvation, are at the root of the poblem. The true causative factor is (at least according to the current paradigm) the lack of a sufficient and constant supply of readily available energy (we are not talking about leafy greens and chicken breast, here!).

Evidence against the "body composition" hypothesis: After a surgical reduction of the stomach volume even obese women can develop amenorrhea

The most convincing evidence for the so-called "energy availability hypothesis", specifically in view of the hormonal aspects of the athlete triad, comes from a 1999 study on the short- and long-term outcomes of a surgical reduction of the stomach volume in severely obese women. Due to their artificially induced physical inability to consume adequate amounts of energy, these women, who were even after they had lost massive amounts of body weight still obese (BMI > 35!) developed amenorrhea (Di Carlo. 1999).

In this context, Anne B. Loucks who worked in the Department of Biological Sciences of the Ohio University in Athens, back in 2005, points out:

"Interest in the body composition hypothesis was rejuvenated several years ago by the discovery of leptin. Because leptin is secreted by adipose tissue cells, it was originally thought to signal information about the size of body fat stores. Rapid and profound declines in leptin were soon observed in response to fasting and dietary restriction, how-ever, and similarly extreme increases were observed in response to overfeeding and refeeding after energy restriction, all before changes in adiposity could occur. These observa-tions led to the revised hypothesis that leptin actually signals information about dietary energy intake. Since then, however, we have shown that the level and diurnal rhythm of leptin actually depend on energy availability (defined as dietary energy intake minus exercise energy expenditure) and that exercise itself has no suppressive effect on leptin beyond the impact of its energy cost on energy availability." (Loucks. 2005; my emphases)

In other words, the same hypothesis that initially pointed towards the amount of leptin secreting adipose tissue as a regulator of the hormonal balance in amenorrhetic women (the "body composition hypothesis"), does now, that it appears clear that energy availability and not body fat stores determine the secretion of leptin, clearly indicate that body fatness is a subordinate (as being the consequence of constant dieting) indicator of a persons susceptibility to suffer from hormonal imbalances, at best.

For similar reasons, the "stress hypothesis" which points with a finger at the exercise induced increases in cortisol is bullocks, as well. After all, those increases in cortisol and catecholamine expression are - just like low leptin levels - a necessary and healthy adaptation to the absence of a constant and adequate supply of energy. Without the glucocorticoids (just in case you still don't get it: "gluco" as in "glucose" <= the stuff everybody is scared about these days) no athlete or anorexic patient would be able to maintain normal blood glucose  - without any cortisol, they would simply die.

Evidence for the "energy availability hypothesis"

Figure 4: 24h-LH profile in healthy women after 5 days of normal (top) as well as calorically restricted (-33, -66, -87%) nutrient intake (arrows indicate meals, the black bar indicates sleep).

In fact, Loucks and her team at the Ohio University have conducted a whole series of studies the results of which support the "energy availability hypothesis" and I want to conclude this first part of the two-part series with the one study that segues directly into part II of this series, which will zone in on the the problem of persistent hormonal imbalances and their dietary and behavioral underpinnings.

In this regard, the profound disturbances in the pulsatile release of luteinizing hormone (LH) from the gonadotroph cells in the anterior pituitary gland, Loucks et al. observed after only 5 days of

• 33% - lower LH amplitude
• 66% - increased amplitude decreased frequency
• 77% - further decrease in frequency + increase in amplitude

calorie restriction, the scientists observed "regardless of whether energy availability was reduced by dietary restriction alone or by exercise energy expenditure alone" (Loucks. 1998) set the scene for a discussion that will be relevant for both, male and female physical culturists.

Don't forget to come back next week for part II!

In other words, if you want more about the role of the thyroid gland, of adiponectin and insulin sensitivity, of ghrelin and growth hormone, of insulin and IGF-1 and the circadian clock and intermittent fasting in the etiology of the athlete triad and which tweaks to your nutrition, exercise and supplementation regimen can help you not end up in a viscous circle that will not just hamper your perfomance, but compromise your physique and physical and psychological well-being, come back next Sunday for part II of the SuppVersity Athlete's Triad Special.

References

• Argente J, Caballo N, Barrios V, Muñoz MT, Pozo J, Chowen JA, Morandé G, Hernández M. Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation. J Clin Endocrinol Metab. 1997 Jul;82(7):2084-92.
• Beals KA, Manore MM. Disorders of the female athlete triad among collegiate athletes. Int J Sport Nutr Exerc Metab. 2002 Sep;12(3):281-93. 
• Boag F, Weerakoon J, Ginsburg J, Havard CW, Dandona P. Diminished creatinine clearance in anorexia nervosa: reversal with weight gain. J Clin Pathol. 1985 Jan;38(1):60-3.
• Di Carlo C, Palomba S, De Fazio M, Gianturco M, Armellino M, Nappi C. Hypogonadotropic hypogonadism in obese women after biliopancreatic diversion. Fertil Steril. 1999 Nov;72(5):905-9.
• Di Luigi L. Does the high performance athlete need hormone replacement? Endocrine Abstracts. 2012; 29: 35.1 
• Figueiro MG, Plitnick B, Rea MS. Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults. International Journal of Endocrinology. 2012, Article ID 530726.
• Golden NH, Meyer W. Nutritional rehabilitation of anorexia nervosa. Goals and dangers. Int J Adolesc Med Health. 2004 Apr-Jun;16(2):131-44.
• Hernández M, Argente J, Navarro A, Caballo N, Barrios V, Hervás F, Polanco I. Growth in malnutrition related to gastrointestinal diseases: coeliac disease. Horm Res. 1992;38 Suppl 1:79-84.
• Hobart J, Smucker D. The Female Athlete Triad. Fam Physician 2000; 61:3357-64,3367. 
• Khan KM, Liu-Ambrose T, Sran MM, Ashe MC, Donaldson MG, Wark JD. New criteria for female athlete triad syndrome? As osteoporosis is rare, should osteopenia be among the criteria for defining the female athlete triad syndrome? Br J Sports Med. 2002 Feb;36(1):10-3. 
• Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. Erratum in: N Engl J Med 1995 Aug 10;333(6):399.
• Loucks AB, Verdun M, Heath EM. Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J Appl Physiol. 1998 Jan;84(1):37-46.
• Loucks AB. Energy availability, not body fatness, regulates reproductive function in women. Exerc Sport Sci Rev. 2003 Jul;31(3):144-8.
• Lu M, Tang Q, Olefsky JM, Mellon PL, Webster NJ. Adiponectin activates adenosine monophosphate-activated protein kinase and decreases luteinizing hormone secretion in LbetaT2 gonadotropes. Mol Endocrinol. 2008 Mar;22(3):760-71. Epub 2007 Nov 15.
• Manore MM. Dietary recommendations and athletic menstrual dysfunction. Sports Med. 2002;32(14):887-901. 
• Mikos AE, McDowell BD, Moser DJ, Bayless JD, Bowers WA, Andersen AE, Paulsen JS. Stability of neuropsychological performance in anorexia nervosa. Ann Clin Psychiatry. 2008 Jan-Mar;20(1):9-13.
• Miller SM, Kukuljan S, Turner AI, van der Pligt P, Ducher G. Energy deficiency, menstrual disturbances, and low bone mass: what do exercising Australian women know about the female athlete triad? Int J Sport Nutr Exerc Metab. 2012 Apr;22(2):131-8.  
• Modan-Moses D, Stein D, Pariente C, Yaroslavsky A, Ram A, Faigin M, Loewenthal R, Yissachar E, Hemi R, Kanety H. Modulation of adiponectin and leptin during refeeding of female anorexia nervosa patients. J Clin Endocrinol Metab. 2007 May;92(5):1843-7. Epub 2007 Feb 27.
• Mont L, Castro J, Herreros B, Paré C, Azqueta M, Magriña J, Puig J, Toro J, Brugada J. Reversibility of cardiac abnormalities in adolescents with anorexia nervosa after weight recovery. J Am Acad Child Adolesc Psychiatry. 2003 Jul;42(7):808-13.
• NCAA® Sports Sponsorship and Participation Rates Report • 1981-82 – 2010-11.  
• Orlandi E, Boselli P, Covezzi R, Bonaccorsi G, Guaraldi GP. Reversal of bone marrow hypoplasia in anorexia nervosa: case report. Int J Eat Disord. 2000 May;27(4):480-2.
• Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, Heiman ML, Lehnert P, Fichter M, Tschöp M. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol. 2001 Nov;145(5):669-73.
• Rguibi M, Belahsen R. Body size preferences and sociocultural influences on attitudes towards obesity among Moroccan Sahraoui women. Body Image. 2006 Dec;3(4):395-400. Epub 2006 Sep 7. 
• Scacchi M, Ida Pincelli A, Cavagnini F. Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa. Front Neuroendocrinol. 2003 Jul;24(3):200-24.
• Scheid JL, De Souza MJ. Menstrual irregularities and energy deficiency in physically active women: the role of ghrelin, PYY and adipocytokines. Med Sport Sci. 2010;55:82-102.
• Schtscherbyna A, Barreto T, de Oliveira FP; Luiz RR, de Abreu Soares RR, Gonçalves Ribeiro B. Age of onset training but not body composition is crucial in menstrual dysfunction in adolescent competitive swimmers. Rev Bras Med Esport. May/June 2012; 18(3).
• Steinberg SE, Nasraway S, Peterson L. Reversal of severe serous atrophy of the bone marrow in anorexia nervosa. JPEN J Parenter Enteral Nutr. 1987 Jul-Aug;11(4):422-3.
• Sundgot-Borgen J. [Physical activity and reproductive health]. Tidsskr Nor Laegeforen. 2000 Nov 20;120(28):3447-51.
• Williams NI, Helmreich DL, Parfitt DB, Caston-Balderrama A, Cameron JL. Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training. J Clin Endocrinol Metab. 2001 Nov;86(11):5184-93.

On Short Notice: Teas & Prostate, Metformin & Amenorrhea, Stevia & High, Omega-3 & Low Cortisol, Aminos & Weight Control, Nordic Hamstring Exercise & 20% More Power!

Image 1: This would be a case where metformin probably won't help you to get your menses back - unless this is just one of your "yous" and you are taking high doses of anti-psychotics, of course.

In view of the fact that I have piled up way more "On Short Notice" items than I can possibly squeeze into one installment, today's news on the right tea (green or black) for prostate cancer, the purported anti-obesity effects of leucine and alanine, which turn out to be inferior to those of whole protein, the anti-amenorrhea and weight loss effects of metformin in women on anti-schizophrenic drug and how this relates to PCOS, the surprising N=1 cortisol-raising, high blood pressure and water retaining effects of stevia, the stress and weight loss reducing effects of omega-3s and high DHA levels in the brain, and an effective yet rarely used hamstring exercise, the "Nordic hamstring exercise", will be complemented by another installment of "On Short Notice" either tomorrow (in case I don't find the time to write the next installment of the Circadian Rhythm Series) or earlier next week... but enough of these organizational matters, let's see what we have in stock, here:

• Differential effects of green and black tea on prostate cancer risk While we are, yet again, only dealing with epidemiological shenanigan in a population living in a, if not the juggernaut of the far east, the >50% increase in hazard risk in the 27,293 men from the Singapore Chinese Health Study Julia A. Montague and her colleagues report for men who drink 1 cup of black tea per day is somewhat alarming (Montague. 2012). The fact that the hazard risk decreases to +17% with more than 2 cups of black tea does yet suggest that this is nothing but a statistic outlier. That said, black tea is (at least based on the results of this study) overall probably as benign as green tea, which is totally devoid of statistical beneficial or detrimental effects on prostate cancer risk in this cohort of normal-weight men in their middle to late 50s.
  This result does by the way not conflict with previous research, which did - if anything - only suggest a "borderline significant" beneficial effect of green tea and absolutely no effect of black tea on prostate cancer risk (Zheng. 2012). Apropos prostate cancer, just in case you missed it I highly suggest you take a look at my brief write-up on the recently published "red meat will give you prostate cancer study" before you decide on whether or not you got to stop eating meat for the sake of your prostate.

• 

  Figure 1: If  ~50g of leucine and alanine /kg chow are good, then 500g of whey are magic; makes you wonder, why you would want to add just one amino acid, instead of more protein, no?

  "Dietary L-leucine and L-alanine supplementation have similar acute effects in the prevention of high-fat diet-induced obesity",  that's the somewhat ill-chose title of a recently published paper by Anne Freudenberg, Klaus J. Petzke, Susanne Klaus from the German Institute of Human Nutrition in Potsdam-Rehbruecke which does not show that the ingestion of l-leucine or alanine, but rather an isocaloric high protein diet version of the high-fat diets the researchers fed their 10-week-old male C57BL/6 mice, prevented them from getting obese (Freudenberg. 2012).
  While the high fat + complete protein mice hardly gained any body fat, the high fat + leucine and high fat + alanine (both diets were "adequate" in protein and contained 100g whey + 60g leucine and 100g whey + 45g alanine, respectively)  got only significantly less fat compared to their peirs on the 100g whey only diet control HFD diet. Now, the high protein mice (500g of whey per kg chow; =5x over baseline) simply consumed less energy, but so did the mice on the leucine and alanine enhanced diets, so that the title of the study is not just misleading, it also disguises the most important result of the study, which is high protein diets keep mice lean.
• "Cure-it-all-drug" metformin helps with anti-psychotic induced amenorrhea and weight gain, as well. If metformin was not (a) no longer protected by patent rights and (b) would not basically work via similar mechanisms as exercise I would really begin to smell fraud over the ever-extending list of pathologies this 1920s medication is good for (this is when it was originally discovered, it took however until 1958 before researchers realized the potentials and a pharma company introduced it to the UK market). New to the list are the negative side-effects women experience in response to anti-psychotic treatments. In a recently documented experiment, 48 women (ages 18-40 years) with amenorrhea and weight gain in response to clozapine, olanzapine, risperidone, or sulpiride (all anti-psychotic drugs administered to treat schizophrenia) received a dose of 1,000mg of the wonder-molecule per day (Wu. 2012). After 2 months 25% of the women had resumed menstruation, after another 2 weeks it were 80% and after 3 months all women were eumenorrheic, again (of the placebo group only 2 resumed menstruating). Instead of gaining another 2kg of body weight, they had lost 2kg and the previously thwarted prolactin, LH, and testosterone levels, as well as the LH/FSH ratio had normalized.
  Probably, some of you may now ask themselves: Will this work for me as well - though I am not taking anti-psychotics? I would love I could answer this question, but aside from polycystic ovarian syndrome (PCOS), where we have a couple of trials in which metformin was used with success (cf. Velazquez. 1998; Bela. 2009; Palomba. 2009), the scientific evidence is scarce and in view of the fact that we know even less about the underlying mechanisms by which risperidone & co cause amenorrhea and weight gain than about the almost magical omnipotence of metformin I honestly can't tell. One thing that comes mind, where metformin is yet very unlikely to of any use is diet or exercise induced amenorrhea (overtraining and undereating), because this form of amenorrhea presents with a totally different hormonal profile, with low levels of basically all reproductive hormones.
• Stevia as cortisol promoter? Case study: Bloating, high blood pressure and malaise in a young previously healthy woman. Before I go on, let me briefly remind you that the events that are described in a recent case report from the University of Iowa Hospitals and Clinics may should be regarded with the degree of caution that is indicated whenever we are talking about case reports, specifically because stevia does actually have a pretty decent safety profile (aside from the occasional allergic reactions you will see with almost every foreign molecule you put into your body, obviously).

  

  Figure 2: If you block the 11bHSD2 enzyme that will convert cortisol into inactive cortisone, you are in trouble and a bloated tummy is certainly your least problem, not because "cortisol is bad", as common sense would dictate, but because not being able to manage it is bad (img. Michael. 2008)

  When a 32 year old Caucasian woman presented with generalized edema (feet, hands and face) that had persisted for over six months at her Dr office and was found to to suffer from pre-hypertension (138/88 mmHg) and hypokalemia (3.4 mM/l) that was brought about by a decline in serum aldosterone and plasma renin activity and corroborated by a concomitant  increase in the plasma cortisol/cortisone ratio, most Dr.'s would probably have thought of licorice intoxication. As it turned out, it were neither the glycyrrizinic acid, not the glycyrrhetinic acid from licorice which brought about these problem, but rather the stevia the lady had been using for over 9 months, now. Obviously, the sweetener (from an undisclosed brand) had blocked the 11 beta-hydroxysteroid dehydrogenase Type 2 (11-beta-HSD 2, see figure 2) enzyme that's responsible for the conversion (="deactivation") of cortisol to cortisone - with all the negative side effects of the subsequent 12x elevation of the ratio of active to inactive corticosteroids (Esmail. 2012).
  Now, I am certainly not suggesting that this is going to happen to everyone, but it could well be that the frequent reports of headaches people are developing after a couple of days "on stevia", could also be related to the effects the sweetener has on people with a certain genetic disposition. So, if you get a headache or start holding water like crazy, when you use stevia / stevia sweetened products, first try using a different brand (there have been issues with toxins in some products), make sure you have a pure stevia sweetener and not one with other sweeteners added (thx. to Amit for the reminder about erythritol that's in many products), switch to another preparation, e.g. from pure stevisoids to a a more "natural" extract and if all that does not help, just turn your back on it - you can live without it, I guarantee ;-)
• Omega-3's modulate adrenal activity What many people know from going overboard on fish oil has now been established in a recently published rodent study by Marie Hennebelle and her French (resident) colleagues (Hennebelle. 2012). The researchers fed a group of rodents a totally ALA free energetically restricted diet to produce male rats with brain phospholipid DHA levels that were 50% lower than those of the normal control. The 6 month-old rodents were then subjected to chronic restraint stress (6 h/d) for 21 days. As expected the rodents on the alpha linolic acid deficient diets had a much harder time coping with the torture they were exposed to and showed higher corticosterone levels, more pronounced behavioral abnomalies and slightly more pronounced weight loss in the 3-4 week of the 1-month experimental period. What's intriguing though is the the remarkable stress resistance (one could also say adrenal hypofunction ;-) in the rodents in a third experimental group, who had received an omega-3 enriched diet that boosted their brain DHA levels to 10% above normal: Compared to both the normal, as well as the omega-3 deprived rodents they had ~30% lower cortisol levels during week two and three of the experiment and lost only 50% of the weight their normal and ALA deprived peers did.
  That this is not necessarily a good thing for everyone is probably nothing I have to tell you. After all, the number of people who are hardly functioning due to over-supplementation with fish oil and (as this study would suggest) below normal stress responses is ever increasing. As with so many nutrients and supplements, it thus comes down to specificity and hitting the right ratios for you as an individual, again. And what's most important: Before you even start thinking about "fixing your adrenals" you should first take a look at the various stressors in your life. After all, the aforementioned fatigue is not simply a result of two much fish oil, but of its combination with a lifestyle which simply requires a robust and healthy cortisol response. You would not smoke weed to calm yourself down minutes before running away from a saber-toothed tiger, either, would you?

• 

  Video 1: These young ladies show you how it's done - well almost, you better go a little slower (click image to watch.

  Scientists confirm efficacy of nordic hamstring exercise - up to +20% increase in peak torque! What? You don't know the nordic hamstring exercise - I bet you do, but probably not by this name. Check out video 1 to the right and you will know what the 18 male players from a club in the English professional soccer leagues (mean±SD; age, 22.9±3.6 years; stature, 1.81±0.08 m; body mass 78.0±9.7 kg) did for 1x 2x5, 2x 2x6, 3x 3x6 and 3x 3x8 (sessions per week x sets x reps) during week 1-4 of the study period to improve their peak torque by up to 21% in all assessment conditions (90-61°, 60-31° and 30-0° of knee extension; cf. Iga. 2012).
  What is yet important is that you stick to an adequate temp and don't mess around and hurt yourself. In the study at hand, the velocity of the movement was standardized to 30°/s. If we assume that you go over the full ROM it must therefore take you 3s until your nose hits the ground (if you are afraid to hurt your nose, you may be interested in the SuppVersity EMG Series and the Best Leg + Hamstring Exercises ;-)

I hope you enjoy this more digestible format, having 20 of these items in one installment is - at least in my view - somewhat beside the point. Not that this would not be possible, but if I go by the average attention span of my real-life students, multiply it by 2x to accommodate for your superior cognitive abilities and personal interest in the topic, it appears prudent to call it a day for today. And if can't stand the 24h for the next SuppVersity news to be released, I suggest you simply like the SuppVersity Facebook Wall, where you will find another seven allegedly shorter news-items... about the wheat-allergens in soap (+ scary pic of what can happen, when you use those), for example or the news photo-based cholesterol test (a photo of your hands is all it takes), which is probably going to give the sales of statins another boost.

References:

• Billa E, Kapolla N, Nicopoulou SC, Koukkou E, Venaki E, Milingos S, Antsaklis A, Adamopoulos DA. Metformin administration was associated with a modification of LH, prolactin, and insulin secretion dynamics in women with polycystic ovarian syndrome. Gynecol Endocrinol 2009; 25:427–434
• Esmail S, Kabadi UM. Edema, Enigma: 11 B-Hydroxysteroid dehydrogenase Type 2 Inhibition by Sweetener “Stevia”. Open Journal of Endocrine and Metabolic Diseases, 2012, 2, 49-52.
• Freudenberg A, Petzke KJ, Klaus S. Dietary L-leucine and L-alanine supplementation have similar acute effects in the prevention of high-fat diet-induced obesity. Amino Acids. 2012 Jul 31.
• Hennebelle M, Balasse L, Latour A, Champeil-Potokar G, Denis S, Lavialle M, Gisquet-Verrier P, Denis I, Vancassel S. Influence of omega-3 Fatty Acid status on the way rats adapt to chronic restraint stress. PLoS One. 2012;7(7):e42142.
• Montague JA, Butler LM, Wu AH, Genkinger JM, Koh WP, Wong AS, Wang R, Yuan JM, Yu MC. Green and black tea intake in relation to prostate cancer risk among Singapore Chinese. Cancer Causes Control. 2012 Aug 3.
• Palomba S, Falbo A, Zullo F, Orio F Jr. Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr Rev 2009; 30:1–50
• Wu RR, Jin H, Gao K, Twamley EW, Ou JJ, Shao P, Wang J, Guo XF, Davis JM, Chan PK, Zhao JP. Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study. Am J Psychiatry. 2012 Aug 1;169(8):813-21. 
• Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure while facilitating normal menses and pregnancy. Metabolism 1994; 43:647–654
• Zheng J, Yang B, Huang T, Yu Y, Yang J, Li D. Green tea and black tea consumption and prostate cancer risk: an exploratory meta-analysis of observational studies. Nutr Cancer. 2011;63(5):663-72.