While there has been no definite information published as to who should not take pregnenolone, on theoretical grounds, a few cautions can be suggested. Since pregnenolone (especially at high doses) may (in some people) increase estrogen or testosterone levels, I believe that men with prostate cancer (which may be worsened by testosterone) and women with breast or ovarian cancer (which may be worsened by estrogen) should probably take pregnenolone only with their doctors consent and supervision. Men with high PSA (prostate specific antigen) blood levels (possible indicator for undiagnosed or future prostate cancer) should also proceed with caution with pregnenolone use. Lastly, because of pregnenolones anti-GABA, pro-NMDA action, persons known to suffer from epileptic seizures or who are taking an anti-seizure medication such as Dilantin, Depakote or Tegretol should probably only use pregnenolone with their doctors supervision. Finally, as we age, the body produces ever-less of the enzyme which converts pregnenolone to DHEA. Thus, while supplementary pregnenolone taken during middle age and beyond will produce at least some normalization back toward more youthful (and healthful) levels of other steroid hormones, pregnenolone will not completely substitute for other steroid hormone supplements in those with medically demonstrated needs for various specific steroids ., DHEA, cortisol, estrogen, etc.
The course of GAD tends to be chronic in primary care patients, and GAD may "switch" to other diagnoses, particularly depression and somatoform disorders [14, 15] . GAD is associated with impairments in psychosocial functioning, role functioning, work productivity, and health-related quality of life comparable to major depressive disorder or panic disorder. Patients with GAD and comorbid major depression show significantly greater impairment in health-related quality of life than in either disorder alone. Primary care patients with GAD showed significantly higher annual medical costs than patients without GAD (median $2,375 versus $1,448) and higher mean annual medical costs ($2,138) than patients with other anxiety disorders. GAD is frequently under-recognized in primary care, and only 20% to 32% of patients receive adequate treatment. Suboptimal treatment adds to the health-related quality of life burden of this disorder  .
The attention impairments in MHE are observed on a variety of measures. These include measures of cognitive processing speed involving psychomotor responding, such as the Number Connection tests (NCT), block design test (BDT),the Digit Symbol test (DST), line drawing test, circle-dotting test, serial-dotting test, figure connection test. Impairments on measures of cognitive processing speed and response inhibition that do not require a motor response have also been reported (., with verbal fluency tasks and measures such Stroop test). 22,23 Visuospatial impairments have been primarily reported on block design tasks (which also include a motor/practic component), but also on more pure measures of visuospatial perception, such as line orientation or the Hooper test. Fine motor skill impairments have been noted on measures such as the grooved pegboard task, and on line tracing tasks (the latter also involve visuospatial abilities). 24