Prospective study finds that elevated total and free Estradiol levels in the follicular phase and elevated total and free Testosterone levels in both the follicular and luteal phase are associated with increased breast cancer in women. The risk is for pre menopause in this study. This and several other studies point to serious questions about the massive dosing of Testosterone via pellets, injections, and topicals for libido. We appear to be following the same patter as seen with premarin, provera, now Testosterone in men and this may be the next ball to drop. Is the Testosterone therapy merely producing an environment that feeds breast cancer?
Injectable testosterone shown to increase Estradiol production and negatively influence the E2:T ratio in older, obese men. This is no surprise as age and obesity are known to increase aromatase activity. I am really surprised that no discussion of aromatase inhibition was discussed.
lower Free Testosterone and increased Estradiol through aromatase activity is associated with increased atherosclerosis. This was monitored with Carotid intima-media thickness. This study found an increase associated with low free Testosterone and increased free estradiol levels independent of other CVD variables.
Low total Testosterone, low free Testosterone, and low SHBG associated with increased CRP. Serum total estradiol and free estradiol trended to a positive association, but did not reach statistical significance.
Estradiol found to be associated with Metabolic syndrome in men. This was independent of other confounding variables. Most men, the excess estradiol comes from increased aromatase activity on testosterone.
Diabetes associated with low serum testosterone. This study points to a 4.7 fold decrease. This is accompanied by a 2.9 fold increase in estradiol. Castration worsened this imbalance by decreasing the testosterone level further. Likely the low T and increased aromatase activity aid in the development of diabetic renal disease. Numerous studies have shown that testosterone therapy improves glucose homeostasis.
Study finds that higher BMI and insulin levels associated with decline Testosterone levels. But, so were risperidone and olanzapine in schizophrenic patients. The association between the medications and the BMI and insulin was less in the meds, but still present. The risperidone had a greater association with a lower Testosterone. Increasing estradiol levels correlated with the low Testosterone levels.
study finds high incidence of prostate cancer in those with low Testosterone at the time of biopsy for HGPIN. What is also interesting, is that the authors found a higher SHBG. It is well known that Estradiol increases SHBG. It is also well known that Testosterone to Estradiol in the prostate plays a role in prostate cancer.
peripheral aromatase activity and Testosterone to Estradiol production have central HPA axis suppression resulting in decreased LH and FSH and low Testosterone.
Study finds increased risk of sudden MI in men with low Testosterone and elevated Estradiol. In converse, increased risk is associated with elevated Estradiol in women.
New study shows that obese boys/young men pre and post puberty have up to 50% lower testosterone levels than comparative normal BMI counterparts. Also of note, estradiol levels were not associated with the low testosterone levels.
cross sectional study finds low vitamin D associated with a decrease in SHBG and an increase in free Testosterone; a decrease in estradiol and an increase in DHEA was seen in women. No association with total Testosterone was found. There are studies that show a direct decrease in testicular Testosterone production in men with low vitamin D and decrease in AR function.
total and bioavailable Estradiol associated with increased hsCRP in men age 40-80. Bioavailable is calculated with serum calculated free Testosterone and albumin bound Testosterone.
Several flaws with this study. First, the majority of testing done in the meta-analysis was serum--unreliable. Second, this study flies in the face of many other studies that have shown elevated estrogens contribute to low testosterone in men. Third, this flies in the face of observation. I see over and over again, by lowering a male's estrogen level, he in turn will start producing more Testosterone. And finally, the environmental xenoestrogens have helped to contribute to a all time low of testosterone/infertility rate in men today.
The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
This increase was even more pronounced at 44 d, at 33%
We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial,
which occurred as early as 14 d and was maintained until the end of the trial at 44 d
We first investigated testosterone production after 24 and 48 h of ibuprofen
exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent
(β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time
The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early
as 14 d of administration
Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen
administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production
of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection
except in one experiment with DHEA
Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory
effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine
cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of
steroidogenesis.
Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence,
expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
A previous study reported
androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of
every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
the changes in gene expression indicate that the transcriptional machinery behind the endocrine action
of Leydig cells was most likely impaired by ibuprofen exposure.
Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
The decrease in the free testosterone/LH ratio resulted primarily
from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen
exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted
from ibuprofen’s direct antiandrogenic action
AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from
gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the
Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
a chemical compound, through its effects on the signaling
compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in
the adult human
The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise
response in muscles by repressing transcription
Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates
(41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes
in peritubular cells was also affected
short-term
exposure
In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated
hypogonadism (4), an entity associated with all-cause mortality
compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
an inverse relationship was recently reported between endurance exercise training and male sexual libido
AMH concentrations are lower in seminal plasma from patients with azoospermia than
from men with normal sperm levels
inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical
compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
after administration of 600 mg of ibuprofen to healthy
volunteers
post menopausal estradiol in women associated with pro-inflammatory state. SHBG was associated with a decrease in the inflammatory cytokine biomarkers. Postmenopausal women were found to have an increased Testosterone to estradiol ratio.
aromatase inhiibition via anastrozole decreased Estradiol and allowed for an increase in Testosterone production. Estradiol has a negative feedback at both the hypothalamus and the pituitary.
Rat study finds balance of DHT and estradiol play important role. The production of DHT removes Testosterone from the pool to make estradiol through aromatase activity.
Estradiol in mice predisposed to Lupus have increased inflammation and characteristics of Lupus. In contrast, Estradiol in those without predisposition, do not. Clearly this is an inflammatory signaling problem. Studies have shown an Interferon gamma signaling deficit in those with Lupus.
Testosterone decreases the above inflammation signaling.
The genesis of cancer is complex. To simply say that cancer is genetic is both niave and uninformed. This study displays the complexity of the timing of hormones and cancer genesis. This rat study found that Estradiol added to Testosterone increased "markedly". Estrogen plays a role in the genesis of prostate disease. However, this varies among individuals. The response of prostate cancer to estradiol appears to change according to the progression of the cancer.