A new paper (Patel 2009) says Early postmenopausal women with higher testosterone (T) levels have increased insulin resistance (IR) and cardiovascular risk factors; so to test whether higher T levels are associated with IR, the metabolic syndrome (MetSyn), and coronary heart disease (CHD) , ie whether this translates into increased cardiovascular disease later in elderly women, ultrasensitive testosterone s-T assays were used in 344 women aged 65–98 yr enrolled in the Cardiovascular Health Study CHS, with cross-sectional analyses to examine the associations betweentotal and free T and IR, MetSyn, and CHD. They found a stepwise increase in insulin resistance with increasing total (P =0.0.003) and free T (P = 0.02) level and a corresponding decreasein Insulin Sensitivity.. In adjusted models, higher levelsof both total and free T were strongly associated with abdominalobesity and high fasting glucose, the two MetSyn componentsmost strongly linked to IR. After adjustment, women in the topquartile of total T levels had a 3-fold greater odds of MetSynand CHD(odds ratio 3) thanthose in the lowest quartiles, whereas free T was not significantlyassociated with MetSyn or CHD.
What clinical relevance does this crossectional observational study have in management of postmenopausal women? Observational studies say nothing about cause and effect.
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.
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 over a decade 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 is that the higher the anabolic hormone (testosterone and vit D) levels, the greater their strength and with 2/3 reduction in falls- which are the greatest risk factor for fractures. – with the extra vitamin D3 further reversing obesity.
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 conclude “In 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.”
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.”
Despite the fact that obesity is endemic in women, 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 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. .
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 Insulin Resistance, Metabolic Syndrome, and Cardiovascular Disease on balanced testosterone replacement in women with relative testosterone/ estrogen deficiency.
So, so far there is no evidence that the natural higher serum testosterone 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.
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