Tag Archives: PCOS


neil.burman@gmail.com 13 June 2010


Friday’s BBC newsbite  is about preteen UK girls’ high meat intake  association with earlier periods and breasts as well as obesity, and thus more infertility- polycystic ovary syndrome PCOS- and breast cancer .  

Is the link directly the increased protein intake? or increased cooked fat intake?  or increasing carbohydrate load due eg to cornstarch stuffing of the food chain? or increasing stress? or the environmental feminization of nature by ubiquitous estrogenic pollution?  

 Or is it due to  anabolic steroids used  used to increase profits, promote fast  livestock growth? Use of the  latter has been banned in Europe for over a decade, but is believed to be still prevalent in Europe in at least 10% of meat production due to difficulty in detection.     

  The FACS paper  on South Africa  anabolic steroid use in meat  dated  2009 – with the   only reference paper from USA  2000 – says “Public concern over the safety of South African meat and meat products which might contain hormones has increased, particularly since the use of hormones in meat production is not permitted in Europe (EU). The fact is, for decades in South Africa, almost all abattoir meat has been produced with the aid of hormones, and it is known to be a completely safe practice.”  

How can FACS – claiming to represent “ the South African National Consumer Union , the Association of Dietetics , the Directorate of Food Control of the Department of Health and professional representatives of other consumer-friendly organisations” support anabolic steroid use in the meat industry as ‘a completely safe practice’?

 A new paper from Europe  confirms the increasing problem of illegal anabolic ‘Hormonal growth promoting agents in food producing animals’  in the meat industry there. 

 The doyen of falling    fertility Professor Nils Skakkebaeck (in print on Pubmed since 1968) last reviewed environmental including hormone  meat contamination  in 2007,  and endocrine disruptors in general  last month,  after Deborah Cadbury’s exhaustive seminal 1997  review of his and others’ infertility work in The Feminization of Nature.  

 Our own andrologist Prof MS Bornman of Pretoria  has done extensive work on infertility and testicular cancer  in northern South Africa, the latest on association with industrial estrogen pollution in game –  eland-  there. 

 The Cancer Prevention Coalition  has recently filed a petition with the USA FDA that  ‘A Ban on Hormonal Meat is Three Decades Overdue’.

 It is just 25 years since Margaret Attwood’s chilling prophetic novel The Handmaiden’s Tale on male infertility in America.     And 15 years since the EU banned growth hormones in the meat industry. The saga is related in detail in Beef Hormone Controversy. which highlights yet again the power of (EU) voters’ voices to force government to act on the public’s  concerns;  whereas 25 years later Canadian and USA Industry still sway their governments to ignore concerns and evidence.

So is the livestock industry in South Africa, Australia, UK -EU  and North America- indeed everywhere-  still feeding us and especially our youth anabolic steroids in meat?   Human greed  knows  no limits.

It is in  the lifespan of some still alive  (from before my father’s birth in 1896) that  the use of commercialized  sex  hormones moved from  rejuvenation  and sexuality to in the past 50 years human birth control,  sex change,  bodybuilding , competitive gamesmanship, and speeding up meat  production. 

 Their increasing use is undoubtedly  contributing to the  feminization of nature, cancer burden,   and extinction of many species.  But perhaps their widespread use in the food chain  will peacefully reduce what some consider a plague, dangerous surfeit  of humans on Earth, if not just softening, more dimorphism- feminization – of male aggression and rapacity. An ironic twist to the age-old practice of male castration.


What evidence is there that higher Testosterone Levels in Women CAUSE Obesity, I.R., Metabolic Syndrome, CVD or Cancer?


A new paper (Patel 2009) says   Early postmenopausal women with higher testosterone (T) levels have increased insulin resistance (IR) and cardiovascular disease CVD  risk factors; so  to test whether higher T levels  associate with IR, the metabolic syndrome (MetSyn), and coronary heart disease (CHD) , ie whether this translates into increased CVD later in elderly women,    ultrasensitive testosterone T  assays were used  in 344 women aged 65–98 yr enrolled in the Cardiovascular Health Study CVH,  with cross-sectional analyses..   They found a stepwise increase in  IR with increasing total (P = 0.0.003) and free T (P = 0.02) level. In adjusted models, higher levels of both total and free T  strongly associated with abdominal obesity and high fasting glucose, the two MetSyn components most strongly linked to IR. After adjustment, free T was NOT significantly associated with MetSyn or CHD.

This CVH study was in 5201 folks from 65-101yrs  ie mean age ~72yrs . They  were overweight – mean waist 93cm, BMI 26kg., +- 25% with metabolic syndrome.

What clinical relevance  does this crossectional observational study have  in management of postmenopausal women PMW?  Observational studies say nothing about cause and effect.

The alarming finding from   that CVH  study is that the more frequent the use of aspirin  , the higher the rate in women of ischemic stroke (O.R 1.6) but especially hemorrhagic stroke (O.R 4.0) . SO ELDERLY  WOMEN SHOULD NOT BE PRESCRIBED ASPIRIN-   stick to fish oil and EDTA.

We have known for   decades that increasing obesity  in women  associates  with increasing estrogen (from fat) and testosterone (from ovaries). – as in PCOS, as in PMW, the only effective endogenous defence mechanism women can mount against increasing obesity (and thus insulin resistance, prediabetes)  is to increase luteal testosterone output -ie it requires ovaries..

But the overwhelming positive spinoff from CVH is  that the higher the anabolic hormone (testosterone and  vit D) levels ,  the greater their strength and  ( 2/3)  reduction in falls– with the extra vitamin D3 further reversing obesity. Falls  are the greatest risk factor for fractures. .

OVARIAN CANCER? A year ago a Queensland group (Olsen ea) found that Women who had ever used testosterone supplements had a a 3.7fold  increased risk of ovarian cancer;” but they make no claim about cause and effect. In 1591 cases with ovarian malignancy they found only 11 who gave a history of testosterone use, compared to 4 of 1501 controls who had used testosterone, but they gave no breakdown on how many used physiological ie safe  parenteral balanced  physiological testosterone as opposed to unphysiological ie risky exposure. As they concludeIn summary, we found no consistent evidence for a role of androgens in the aetiology of ovarian cancer, overall or by subtype, and thus our findings do not support the hypothesis that androgen-related disorders increase the risk of ovarian cancer.”

As opposed to virilizing ovarian tumours which secrete excess testosterone, the rarity of testosterone causing ovarian cancer is illustrated by there being only 3 cases reported of  ovarian cancer in a female-to-male transsexual treated with male dose testosterone (Dizon  2006, Hage ea 2000.) despite the increasing use of testosterone for such gender change let alone for female androgen insufficiency in women with ovaries. However, Louis Gooren’s group did describe in 1991  PCOS-changes in the ovaries removed at hysterectomy after a mean of 21 months of testosterone therapy in 12 of  17  female to male transsexuals. Unsurprisingly, no cases have been reported of women athletes developing ovarian cancer after years of testosterone abuse – presumably such reports were suppressed in the Eastern Block countries where such ruthless  practice was rife.

.Despite the fact that  obesity is  now endemic, associated with numerous diseases, especially vascular disease,  diabetes and  cancer, and that PCOS is by far the commonest associate of female hyperandrogenism, there is no evidence that PCOS ie  spontaneous hyperandrogenism is associated with increase in any cancer.  This suggests that moderate hyperandrogenism in women  is indeed protective against cancer since it mitigates the cancerogenic effect of obesity and diabetes.

2 years ago Braunstein from the Cedars-Sinai reported “a significant relationship  between total and free T and the presence of coronary artery disease after adjustment for the effect of E2“.  Similarly, no evidence is adduced for cause and effect. Observed subjects were very high  risk-  mean age 65yrs, obese (mean BMI 30kg),  70% on aspirin, and half had had hysterectomy.  As they conclude “One potential problem with the current study is that the results were obtained in a highly selected group of women undergoing coronary angiography for suspected ischemia and who had a high CAD risk factor burden, raising the possibility that these findings may not be relevant to broader groups of women.”

No studies and no clinics on any continent  have ever reported link  between balanced physiological parenteral depot testosterone (up to ~10mg/week) – depot estradiol  replacement  (up to ~1mg/week) and increase in any cancer  or IR, Met Synd, and CVD  on  balanced  T replacement  in women with relative T/E   deficiency.  The same goes for the use of appropriate parenteral physiological testosterone replacement in men with testosterone deficiency. .

So thus  far there is no evidence  that the natural higher serum T concentrations within the range found  in younger or older women (up to ~6nmol/L) CAUSE overweight/ obesity Insulin Resistance, Metabolic Syndrome, cardiovascular disease or cancer. This is not surprising since our experience bears out the extrapolation to women from the data of Nieschlag and Behre (1991 et seq)  that testosterone level after the proportionate  depotestosterone cypionate or enanthate  ~10mg dose sc/ week will average around 2.4nmol/L .



only 5 weeks since our last review,

twelve  new papers further confirm the supremacy  of the galega plant extract  metformin as the most important chronic preventative drug ever, alongside other natural nutrient supplements eg – fish oil, vitamin C, the human hormones  vitamin  D, sex hormones, thyroid:


1. Aled Rees’ team at Wales’ Cardiff  University  show in a randomized controlled double-blind RCT that obese  women with PCOS (hirsutism and failing periods) even at a mean of 30 (18-35) years have evidence of insulin resistance and early vascular disease; which at their weight around 96.5kg and BMI 35kg/sqm, with waist around 108cm and hips around 120cm, is reversed by metformin: 1500mg/day compared to placebo for 12 weeks  reduced weight by 2kg, body fat by 2.5%, waist by 5cm, bloodpressure by 7% and improves circulation; with 18% fall in insulin resistance (HOMA-IR) , 15% fall in free androgen index, and 21% fall in the testosterone: estradiol ratio.

2.A Tehran University Iran (Ashrafinia) RCT (although not big enough to be statistically significant)  shows that metformin is 81% better than ovarian diathermy in treatment of PCOS inferrtility.

3. and the  German University Erlangen open study –Effect of Metformin Treatment for 2 Years without Caloric Restriction on Endocrine and Metabolic Parameters in Women with Polycystic Ovary Syndrome-(Oppelt)  similarly showed that  even without calorie restriction,   while “no significant changes in body mass index or HOMA-IR were observed,  on metformin  a significant decrease in hirsutism, in fasting and 2-h insulin levels was observed,  with a significant increase in sex hormone-binding globulin (SHBG) levels, while total testosterone (TT) levels and the free androgen index decreased significantly; with significant improvement in lipids.”

These bear out what this column has previously  reported about the superiority of metformin over surgery or other (designer synthetic) hormone therapy  from the work of eg Charles Glueck and  Louis Ibanez for PCOS metabolic syndrome and infertility. .

Diabetes :
4. A retrospective Massachussets study (Brownstein) shows again that  in recent diabetics, the relative risk for heart attack with rosglitazone Avandia  was  120% higher  compared to metformin or  pioglitazone Actos;
5. and a retrospective UK study (Tzoulaki) that pioglitazone was associated with reduced all cause mortality compared with metformin.
But these are retrospective studies, not controlled prospective trial.  they do not mention  the cardinal fact that  pioglitazone does the opposite of metformin, it increases body weight,  heart failure and fracture rate;  and that after a decade of intensive pioglitazone  promotion and trials, there is no evidence from hundreds of direct randomized controlled trials in at least 26 000 patients  that pioglitazone reduces all-cause mortality and chronic diseases  including cancers by a third, as metformin did in the longest RCT ever, the 20year UKPDS, and in many other studies.  No modern designer drug does what metformin does .
6.A systematic review in children by University Sydney shows that   metformin for about 6 months lowers insulin resistance and overweight.
and in new rodent studies:
7. from Russia, (Anisimov ea)  metformin significantly reduces cancer risk, increasing lifespan by 8% and breast cancer latency by 13%, halving breast cancer transplantability and with melatonin reducing Ehrlich tumour growth by 40%  ; 8. from North Carolina (Quaile) that the minimum toxic dose of metformin in the diet was equivalent (by the usual average 10:1 conversion for faster rodent metabolism) to between 60 and 120mg / kg/day ie about 4-8gm /d  for about 5 years in humans;

9. and from Poland (Labuzek) that metformin shows beneficial effects in experimental models of neuroinflammatory diseases like Alzheimers.

10 In June an international team   (Jiralerspong ea Texas/ Germany) showed in an observational study that Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a 3fold higher pCR pathological complete response rate (24%) than do diabetics not receiving metformin (8%) . In response,  Garcia & Tisman from California point out yet another mechanism for this improvement,  that metformin induces malabsorption deficiency of both folate and especially metabolically active holotranscobalamin; which is  potentiated by neoadjuvant chemotherapy induced lowering of holotranscobalamin., despite apparently normal measured  total B12 levels.

This reminds us of  three  truisms:
diabetics are more prone to cancer and neuropathy and homomocysteinemia, these  need to be more concientously screened for;
diabetics are even more in need of all micronutrient supplements as antioxidants, insulin sensitizers, anti- glycation agents, nitric oxide providers, neurotropics;
and where cancer occurs, the golden rule is that no supplements  (other than metformin) should be given until conventional (radio/chemo/surgical) therapy  of the cancer has been commenced or refused. Folate and B12 should not be withheld simply because they may antagonize one link in the carcinogenic chain- there are dozens of dietary adaptations and micronutrients that are major anticancer adjuvants. without putting the patient at greater risk from vascular and osteoporotic disease than ever she was from cancer.
So that is at least 2 new studies a week confirming metformin’s supremacy.
Hence the obligation grows to prescribe as anchor support metformin to comfortable safe tolerance for life not just in all diabetics but also in all overweight people- starting if necessary in childhood-  who cannot maintain both optimal BMI, blood sugar and lipids off it.  And for protection against cancer and Alzheimers and vascular disease, to all perhaps over 50years.

But of course, global  metformin / galega use  along with other supplements  (from vitamins- minerals to all the other useful natural biologicals and insulin sensitizers- – from arginine to zeaxanthine including appropriate sex hormone replacement SHRT)-  will do away with perhaps 90% of the grounds for modern prescription drugs and non-post-trauma surgery/procedures, and much infertility and obstetric problems.  Painful shrinkage for the massive and toxic new -drug / disease/ hospital/hightech industry and the millions of workers it employs as lobbyists and marketeers. Hence redoubling of the effort by the Disease Industry and most governments  to suppress such natural prevention at all costs, by buying over politicians, medical regulators and powerful medical associations and patient groups..


It’s just a month since this column reviewed the only “drug” that is (like fish oil)  a universal panacea: A STUDY OF THE CENTURY: METFORMIN PREVENTION OF THE TIMEBOMB  DIABETES.

Now a  new study from Univ. N Carolina (Cantrell ea) shows that metformin is not just major benefit against prostate and  breast cancer but also against endometrial (womb) cancer.

de la Monte and Wands (2005-2008)  from Brown University RI crystallize what has been obvious the past decade, that Alzheimers disease- they call it type 3 diabetes mellitus-  is not an inevitable part of aging but  is as much a product of insulin resistance – the  overweight  (fast food- couch potato- stress) pandemic- as are all the other interrelated  common diseases that constitute premature aging;   and therefore even more reason for everyone  to take galega/ metformin or other insulin sensitizers preventatively from as young as possible.

And a new novel study from Colorado University (Nadeau ea) again demonstrates that even juvenile type 1 insulin dependent diabetics have insulin resistance and need metformin and all the other anti-AGES agents  as well.

The McMaster University (Lemon Boreham and Rollo) landmark Supermouse Trial   5 years ago used a a novel model of our current self-induced obesity pandemic- a transgenic  mouse-  to show  that unlimited access to ‘balanced’ chow grows, learns, sickens and kills  far earlier than normal mice – which even in a lab environment neither overeat nor get lazy nor fatten. .   But 10fold increase in all the scores of evidence-based conditioned essential micronutrients (that deplete as we age) greatly increased the supermice’s learning, healthspan and lifespan. Such supplements include many powerful  natural insulin sensitizers.

Emory Univ Atlanta (Narayan and Williamson 2009) claim in a new review that “trials show that lifestyle intervention reduces diabetes incidence by over 50% and is more efficacious than metformin. But neither experience nor realistic long term  trials show this.

Now a  followup report from the landmark Diabetes Prevention Program DPP in the USA ( first reported in 2002) in  middleaged overweight laizzez- faire volunteers (not patients) gives the longest ever controlled observation study (the DPPOS) – a mean of 8.5 years- of the benefits of strenuous lifestyle+ diet (LSD) alone for 8.5yrs, or with metformin  for 8.5yrs plus  strenuous LSD added for 5.7yrs,   or just adding LSD  for 5.7yrs  to the initial placebo laizze faire group.
The outcomes are impressive:
The original placebo group (on average attempted diet + exercise) had a diabetes incidence in the first 2.8years of 11.0 (9.8-12.3)% ie per 100 patient years (ie an enormous 5.5% a year, or perhaps 55% over 10 years); with LSD for the next 5.7 yrs their incident  diabetes halved to 5.6 (4.8-6.5)% ie perhaps 1% a year- a reduction of about 82% .
The original LSD group after 2.8yrs had had a new diabetes rate of 4.8%; continuing this regime for 3 times as long saw their new diabetes rate climb to 5.9%;
but the just metformin group– who had new diabetes rate of 7.8% – with added LSD for 5.7yrs saw their new diabetes rate fall further to 4.9% (compared to 11% on placebo and routine counseling) – and unlike the LSD-alone group, they maintained their original weight loss, in fact those over 60years maintained a further 2kg weight loss. Compared to the original placebo group diabetes incidence of 55% over 10years, metformin plus sustained exercise lowered new diabetes to about 8,9% over 10years ie 84% reduction in risk.

Thus this unique 10year study confirms that adding even lowdose metformin to LSD more than halves the incidence rate compared to  the average laizzez- faire patient on feeble diet-exercise alone, and maintains better fatloss than either mild or strenuous LSD alone. We know from clinical experience that titrating metformin to tolerance can maintain weight loss of 8% -provided it is not combined with psychotropes that hugely increase weight gain..

Thus there is every reason to always add metformin cautiously from the beginning to diet-exercise counseling in every overweight patient battling to lose fat and regain fitness, to abolish the lethal risks of metabolic syndrome and its diverse consequences- diabetes, cancer, cardiovascular disease, arthritis, dementia  etc.

It is common knowledge that less than 10% of patients maintain significant weight loss on any diet and exercise regime- it goes against human nature. The DPPOS confirms that preventative metformin to tolerance plus sensible diet and exercis is  the only regime that maintains weight loss and thus improves all health- drastically lowers all-cause premature disease and mortality.

No heavily marketed  designer “appetite/weight suppressant” drugs remotely achieves all the benefits of metformin, a unique  anti-glycation antioxidant,  appetite and weight suppressant, and anti-cancer, -stroke, -vascular , -infection, -arthritis , -infertility, and -dementing- disease natural nutrient. Hence as previously described, Big Pharma and the Disease Industry do all they can to suppress it’s preventative use (including having Regulators threaten us) , since no modern designer drug can compete. A short-term study (3 months) like the new University California Davis trial (Banazewska ea) (of statin versus metformin in PCOS) says nothing about the longterm benefits that matter to patients– not the Drug Industry whose concern is shorterm profit at all cost.