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

neil.burman@gmail.com

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 .

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

  1. Pingback: TESTOSTERONE AVAILABILITY IN SOUTH AFRICA « Healthspanlife – the Official Life! Blog

  2. I read this piece of writing fully regarding the comparison of most recent and earlier technologies, it’s remarkable article.

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