Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
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Unexpected test results... I would be grateful for some guidance

Discussion in 'Diagnostic Guidelines and Laboratory Testing' started by Bluebell, Jun 28, 2013.

  1. Tulip52



    Actually, they are not so abnormal, mine have been like that, just keep an eye on them. As for pernicious anemia, my mother had this as well as celiac diseae and vitiligo. Doctors normally check antibodies to intrinsic factor and anti-parietal cell antibodies with methylmalonic acid and B12. You have to have the antibodoes to develop pernious anemia because it attacks the parietal cells in the lining of your gut.

  2. Bluebell

    Bluebell Senior Member

    Hi Tulip52/Linda,

    Thank you for sharing your experience and that of your mom!

    Having large red blood cells seems to be called macrocytic anemia. From Wikipedia: "Macrocytic anemia is not a disease in the sense of having a single pathology, but is rather a condition. As such, it is the class name for a set of pathologies that all produce somewhat the same red blood cell abnormality. Many specific pathologies are known which result in macrocytic-type anemias. Some of these produce slightly different sets of appearances in blood cells that are detectable from red and white cell morphology, and others are only detectable with chemical testing."

    Megaloblastic anemia is a subset of macrocytic anemia, and this can be caused by not having enough B12 or folate (based on several different reasons for the vitamin deficiency).
    "Especially common causes of macrocytic anemias are the so-called megaloblastic anemias, in which cells are larger because they cannot produce DNA quickly enough to divide at the right time as they grow, and thus grow too large before division. Causes for the DNA synthetic problem range from lack of certain vitamins needed to produce DNA (notably folate and B12), to poisons or inhibitors of DNA replication, such as some kinds of antiviral drugs and chemotherapeutic agents."
    To be diagnosed with this condition, the patient does not have to have antibodies to intrinsic factor.

    Megaloblastic anemia is sometimes also referred to loosely as pernicious anemia (here is an example of where both names appear to be used by a hospital at Stanford University: However, within the text, they say that "pernicious anemia is a type of megaloblastic anemia"). "Pernicious anemia" seems to be a term that is not used very precisely in medicine today, because I've seen it used to describe megaloblastic anemia in several sources, but I recognize that I was using it sloppily above when I referred to "megaloblastic/pernicious anemia", because I am not sure if I have a problem with intrinsic factor in my gut, although it is possible.

    The MCV result for megaloblastic anemia has been raised in the last couple of decades, but even sources today list an MCV of over 95 as being one of the indicators of it: "Increased mean corpuscular volume (MCV, >95 fl)"

    I'm not saying that I do have megaloblastic anemia and that I would be diagnosed as such by a mainstream doctor, but for many years I have had a raft of symptoms of B12 and/or folate deficiency, and my recent result of 96 MCV indicates to me that my red blood cells are not as healthy as I would wish.

    I have high hopes that stopping the artifical folic acid and high does of cobalamin that I was taking prior to finding out that I'm compound heterozygous for the MTHFR mutations, and starting the methylation supplements of natural folate and natural B12, will help fix so many areas of my health!

    I can already see that stopping my prior supplements that had folic acid in them, and stopping eating foods that are fortified with folic acid, both of which I did about 10 weeks ago now, has helped my thumbnails a LOT. The newest 1/3rd of an inch on both thumbnails is so much less bizarre-looking! :balloons: The new growth does not have the "fir-tree" appearance of the "Median canaliform dystrophy of Heller". The new growth has some ridges of the "Beau's Lines", but the newer ridges are much flatter than the ones in the top portion of my nails. This has come about, even without taking any natural folate/B12 supplements yet.

    (I wonder if some people who feel better after going gluten-free are actually feeling better because they've stopped ingesting so much artificial folic acid, and it's not to do with the gluten in all cases.)
  3. rlc

    rlc Senior Member

  4. Bluebell

    Bluebell Senior Member

    Thank you rlc, it's always good to consider every scenario.

    On that list of 102 causes are a lot of types of anemia, vitamin deficiencies, and digestion problems. Also many liver problems (liver problems can cause a high result on the CA-125 too). And hypothyroidism is on that list - it seems to affect so many things.

    I read earlier today of some health issue that I've got (though it's entirely slipped my mind what it was) that pressures the red blood cells to become smaller, and I wondered if maybe that opposing force is keeping my red blood cells a little smaller than they'd otherwise be.

    It's remarkable how there are so many complex layers, emergency measures, compensations and redundancies in our physical processes. Nature is miraculous!

    On a prosaic level, I read last week that 1/3rd of our hair is controlled by a certain thing (I think the adrenals; but I don't really remember, and I don't know if it was in a reliable source or just a random blog or something -- the idea does sound a little far-fetched) and in the past 2 months I've probably lost 1/3rd of my hair - I'm grateful to the other 2/3rds for hanging on in there, and possibly (?) being reliant on other physical systems for their sustenance/health.
  5. Bluebell

    Bluebell Senior Member

    This posting will be relatively long, but I wanted to share some excerpts from some of the research I've done on the CA-125 test, and explain what I've decided my next step will be.

    I have one question for anyone here who may have knowledge about this area of testing, which I'll put in bold type below.

    (If you are new to my story, my health background, the explanation about why this CA-125 test was an unintentional part of my recent bloodwork, and my reasons for not having seen a gynecologist immediately about these results are explained earlier in this thread.)

    Main points:

    1. I have a familial link to this kind of cancer.
    My grandmother died in her mid-60s of endometrial cancer. I have now learned that endometrial cancer and ovarian cancer can be linked in some families. 10% of ovarian cancer has an identified familial link. Additionally, a high result on the CA-125 test can indicate endometrial cancer as well as ovarian cancer.
    My female first cousin (sharing the same grandmother as above) had an ovarian tumor in her 30s and when they did surgery, they ended up doing a complete hysterectomy. At the present time, I do not know why that was.
    My 23andme results say that I do not have the BRCA breast cancer genes that they screen for, but they only screen for, I think, 2 out of 150 of them.

    2. My first test result of 314.9 is really high, and is a real cause for concern.
    When non-malignant conditions (such as endometriosis, hepatitis, cirrhosis or benign tumors) give higher-than-normal results on the CA-125, those results are still usually below 65, and they are almost always below 100 or 200.
    98% of women, even pre-menopausal women, who have results above 53/65/100/200 are found to have a malignant condition - for the references on this, see below.
    (I do realize that any particular test result can be due to a random fluke, an error, a mix-up, a labelling problem at the lab, a data-entry problem, etc.)

    3. Even if a high result on this test is not due to cancer, almost all of the other conditions that a high result can indicate are noteworthy and probably need to be treated (see list of them below). A high result (across repeated CA-125 tests) is almost never due to something normal and minor that can be ignored.

    4. The typical investigation into a high CA-125 result by a doctor is: repeat the CA-125 blood test one or more times, manual gynecological exam, ultrasound, CT scan, exploratory surgery. Only surgery and biopsy can be conclusive about whether there is ovarian cancer or not. The other tests may not be helpful in determining what the problem is exactly. Many doctors steer high-risk patients to exploratory surgery, just in case. There are complications from this surgery in 2 to 3% of patients, even if no cancer is found.

    5. It has been shown in a large longitudinal study that early discovery and treatment of ovarian cancer surprisingly did not increase mortality figures or life expectancy overall. However, it caused increased worry and stress, healthcare expenditures, and medical procedures (including risky surgery). Thus, the recommendation is that this test not be used for screening of ovarian cancer in women who do not already have physical symptoms of such cancer, except in certain cases. (There is a new large trial going on in the UK now to look at the benefits of screening certain high-risk populations.)

    6. If the CA-125 test is repeated and the result is higher the second time, this indicates that other medical investigations into the possiblity of cancer must be started. If the result is the same as before and there are no other symptoms of cancer, a series of tests can be done subsequently (like every 3 months - "watchful waiting"). If the result is lower than before, it might indicate that there was some kind of error with the first test, or that the health problem is not a malignant one, and again, a series of blood tests can be scheduled to keep an eye on it.

    7. As my next step, I have decided to take the test (ordering it for myself from one more time. Having a second test immediately is probably what any MD would recommend doing, if I went to see a doctor first. I will do the test 6 weeks after the last test was done, in order to be at the opposite point in my menstrual cycle (this 6-week timing was recommended by Dr. Bast, the founder of the test, in one of the references I quote below). That blood draw will be 2 weeks from now.
    After I get the results of the second test, I will have more information on which to base my decision about what to do after that.

    8. Further information about my health, which has occurred to me may be relevant to the CA-125 result. Duh! (My last doctor was so blase about this, that I just kind of mentally filed it under "?")
    Aside from the suspected endometriosis (first suspected by an MD when I was 21, but at that time I was too young for a laparoscopy so he told me to get one when I was married and preparing to have kids, which sadly has not occurred in my life) that I've had for my whole adult life, I have had some symptoms in the last few years that all is not well with my reproductive system -- I was diagnosed by my last doctor 2 years ago as having had an ovarian cyst that was twisted and probably popped (caused a lot of pain, doubling up on the floor, vomiting, lots of blood outflow, fever) -- but she based this only on my verbal description of what had happened to me (I was travelling when I had the 'attack' and I went to see her about it when I returned), and she did not do a physical exam, blood test, or anything. She said it was normal to have this happen.
    In 2011 and the first half of 2012, the pain I had during my periods would make me vomit at the same time as blood was literally gushing out (sorry to be so frank), and this fun activity would go on for a couple of hours (I told that same doctor about this, and she was not concerned, even though I had iron deficiency which she attributed to the heavy period blood loss, and she was also not concerned about the iron deficiency).
    Thankfully, for the past 12 months I have not vomited due to my periods, and the blood does not gush so much. My serum ferritin is now 51, as well.

    9. I have tried to research the other tumor marker tests, to see if there might be others which could either confirm that something is putting out a cancer marker in my blood, or show that the problem might be originating in a different system in my body, like the liver or gut.
    Because it was relatively inexpensive and worth a shot, this week I took a high-accuracy home pregnancy test to see if I might have hCG in my urine. I did not have any detectable hCG.
    "Some diseases of the liver, cancers, and other medical conditions may produce elevated hCG and thus cause a false positive pregnancy test. These include choriocarcinoma and other germ cell tumors, IgA deficiencies, heterophile antibodies, enterocystoplasties, gestational trophoblastic diseases (GTD), and gestational trophoblastic neoplasms."

    My question to anyone who might know about these things: Are there any other tumor marker blood tests that I can order for myself which might provide some information about what is going on with my health? I am wondering especially about CA 15-3 and CA 19-9.


    (My CA-125 level was 314.9)

    Specific Numbers

    This chart says that the CA-125 "level above which benign disease is unlikely" is 200 (in other words, a level over 200 is likely to indicate cancer).

    In a study of 267 women, 31 had a CA-125 level over 100. Of those 31 women with a level over 100, 97% had cancer (30 women) and 3% (1 woman) had a nonmalignant problem.

    "In order to achieve a false-positive rate equivalent to that in post-menopausal women, i.e. 2%, the cut-off value for pre-menopausal women would be approximately 53 U/mL."
    "Abnormal CA-125 is defined as >53U/mL in Premenopausal Women and >35U/mL in Postmenopausal Women."

    "A CA-125 above 65 in a 50-year-old or older woman is virtually diagnostic of malignancy with a specificity of 98%."

    "If a serum CA-125 level is raised in a premenopausal patient, but less than 200 units/mL, further investigation may be required to exclude or treat differential diagnoses. A level of more than 200 units/mL should prompt referral to a gynaecologist."

    "In cases of ovarian carcinoma, preoperatively determined values of CA 125 in serum are correlated with the extent of the expansion of the disease, histological type of tumor and degree of differentiation of malignant cells. Elevated values UP TO 65 U/mL in serum can also be found in other malignant minors (pancreas, breast, colon, bladder, lungs, liver) and in different benign diseases."

    Of patients that turned out to have ovarian cancer, when their CA-125 was checked before their diagnosis, the "Patients with a Ca 125 level above 100 U/l had a significantly lower three-year survival rate. ...The tumor marker Ca 125 is a prognostic factor. Levels around 100 U/l are indicative of a bad prognosis."

    "given the fact that the cutoff value was set in a way that excluded healthy individuals, any patient testing positive is likely to have a pathology that at a minimum would require diagnosis and in some cases, treatment. In those cases, the result of the test should be considered as beneficial for the patient, regardless of the specific pathology involved."

    "Any condition that causes irritation to the peritoneum, fallopian tubes, ovaries or uterus can cause an elevated Ca-125. It is commonly elevated with endometriosis. I have seen values exceeding 2,000 u/ml in cirrhosis with ascites, pelvic infections and in one case of fallopian tube torsion."

    "2% of premenopausal women without ovarian cancer will have levels exceeding 50 U/mL."

    "In premenopausal women with symptoms, a slightly elevated CA 125 value may be misleading because elevated levels of CA 125 are associated with a variety of common benign conditions, including uterine leiomyomas, pelvic inflammatory disease, endometriosis, adenomyosis, pregnancy, and even menstruation. Nonetheless, extremely high levels of CA 125 may be useful in the evaluation of premenopausal women." And P...y Detection of Epithelial Ovarian Cancer.aspx


    "If your CA 125 level is higher than normal, your doctor will likely repeat the test."

    "Abnormal tests were repeated after 4-6 weeks.
    Persistently abnormal tests prompted a search for malignancy.
    Tests that normalized on repeat were considered false positive."

    "CA-125 is unreliable in differentiating benign from malignant ovarian masses in premenopausal women because of the increased rate of false positives and reduced specificity. This is because an elevated CA-125 level is also found in fibroids, endometriosis, adenomyosis and pelvic infection. When levels are elevated, serial monitoring can be helpful, as rapidly rising levels are more likely to be associated with malignancy than high levels which are static."

    "repeat CA-125 testing should be done at 6 weeks so that the patient, if pre-menopausal, will be at a different phase of the menstrual cycle."
    "The CA-125 is repeated at six weeks if the first test is elevated and the ultrasound is normal. If the CA-125 level on the second test rises 50% or more from the baseline test, then repeat ultrasound is recommended. If the CA-125 value is stable, then the patient would follow the same path as if the first set of tests had normal CA-125 and ultrasound test results. If the CA-125 is rising but less than 50%, then a clinical decision is required, which may include returning in six additional weeks for another CA-125 test and/or repeat ultrasound."
    "If either the TVS or the CA-125 is abnormal, or if both tests are abnormal, consultation with or
    referral to a physician with advanced training and expertise in the management of ovarian cancer, such
    as a gynecologic oncologist, is recommended."
    "There are concerns about the costs of implementing these recommendations as well as the limited
    capacity and access to high-quality TVS by sonographers experienced with evaluation of the ovaries for
    non-obstetric purposes."

    "As with thyroid hormone, each individual has their own normal level for CA 125. Therefore changes in the individual's level are of more significance than the actual value.
    An "abnormal" value must result in a search for the reason. At the very least this will involve a physical exam, an ultrasound, and if negative, a CT scan of the abdomen and pelvis."

    "Three screening tests are currently employed: bimanual pelvic examination, cancer antigen (CA) 125, and transvaginal ultrasound."
    "The pelvic examination does not add additional cost for women who are already undergoing regular gynecologic evaluation and is reliable when done by an experienced examiner, but it lacks adequate sensitivity and specificity as a screening test. It is estimated that physical examination detects only 1 in 10,000 ovarian carcinomas in asymptomatic women."
    "Although the data from this trial provide reassurance that there is no apparent benefit to early detection and treatment of recurrence based upon intensive CA 125 surveillance, there may be specific subgroups of patients who might benefit."
    "Ultrasound is not only expensive but also has limited specificity and sensitivity. In one published study, 4526 high-risk women underwent ultrasound every 6 months. There were 49 invasive surgical procedures: 37 for benign tumors and 12 for gynecologic malignancies. The detected malignancies were ovarian, peritoneal, or fallopian tube carcinoma in 10 women, all of which were stage III, and stage IA endometrial adenocarcinoma in 2 women. The authors concluded that ultrasound was of limited value for the detection of early stage EOC in asymptomatic high-risk women."

    "Beginning in 1993, NCI launched PLCO, using an ovarian screening protocol that combined vaginal ultrasound with simultaneous CA-125 analysis, the latter pegged to a threshold of 35 IU/mL.
    A total of 78,216 postmenopausal women, aged 55–74 years, were randomly assigned to either standard medical care or an intervention arm in which they were referred to their primary-care doctors if their ultrasound results were abnormal (enlarged or cyst-containing ovaries) or if their CA-125 levels were above the 35-IU/mL cutoff.
    The protocol did not specify precisely how women and their doctors should respond to abnormal ultrasound or to elevated CA-125 levels. "Next steps could include repeat ultrasound, repeat CA-125, gynecological exam, or surgery," said Saundra Buys, M.D., a principal investigator in the PLCO trial and a director at the Huntsman Cancer Institute, at the University of Utah.
    When the trial wrapped up after up to 13 years of observation, 212 women from the intervention arm and 176 women from the control group had been diagnosed with ovarian cancer. But ovarian cancer mortality differences between the two groups weren't statistically significant. A total of 118 deaths occurred in the intervention group, compared with 100 in the control group. According to Buys, that discrepancy probably reflects an "overdiagnosis bias" in the intervention arm. "Some of these cancers did not need to be diagnosed," she said. "They weren't going to cause death even if they weren't detected." That's because, as also occurs in prostate and breast tumors, some ovarian cancers are slow growing and might be better left untreated, explains Christine Berg, M.D., chief of the NCI's early detection research group. Moreover, CA-125 levels can rise in response to some benign conditions, including endometriosis, other ovarian diseases, and pregnancy. So, not only did PLCO's screening approach not reduce mortality in ovarian cancer, it also led to many surgeries performed to investigate positive screening results. Of 3,285 women with false-positive results, 1,080 underwent surgical follow-up, and among them, 163 women—15% in all—experienced at least one serious complication. "Some of those surgeries addressed other types of problems, so you can't always call them unnecessary," Buys said. "But we can say that screening the way we did it had no effect on survival, and it did result in surgeries for conditions that turned out not to be ovarian cancer."

    Risk Factors

    "Risk Factors (of ovarian cancer)
    • Increasing age, with highest occurrence in women over 50
    Family or personal history of ovarian, breast, endometrial, or colon cancer (only 10% of cases are linked to family history, however)
    Uninterrupted ovulation (having no pregnancies)
    • Presence of BRCA1 or BRCA2 gene mutations"


    "CA 125 is the essential ovarian cancer marker. High rates are also found in cancer of the endometrium and Fallopian tubes."

    "Malignant conditions associated with elevated CA 125 levels include the following:
    • Epithelial ovarian carcinoma (including fallopian tube and primary serous peritoneal carcinoma): 75%-85% of cases
    • Endometrial carcinoma: 25%-48% of cases
    • Endocervical adenocarcinoma: 83% of cases
    • Pancreatic carcinoma: 59% of cases
    • Breast carcinoma: 12%-40% of cases
    • Lymphoma: 35% of cases
    • Lung carcinoma: 32% of cases
    • Colorectal carcinoma: 20% of cases
    • Squamous cervical/vaginal carcinoma: 7%-14% of cases

    Benign conditions associated with elevated CA 125 levels include the following:
    • Endometriosis: 88% of cases
    • Cirrhosis: 40%-80% of cases
    • Acute peritonitis: 75% of cases
    • Acute pancreatitis: 38% of cases
    • Acute pelvic inflammatory disease: 33% of cases
    • First trimester of pregnancy: 2%-24% of cases
    • Non-disease state: 0.6%-1.4% of healthy individuals"

    Other Tumor Marker Tests

    "All serum tumor markers were elevated in patients with ovarian carcinoma.
    Serum level of CA 15-3 was increased in patients with ovarian carcinoma (median 48.33 U/ml, normal range 0-36), while it was normal in patients with benign ovarian tumors (median 20.67 U/ml; p >0.05).
    CA125 serum values were strikingly increased in ovarian carcinoma (median 264.16 IU/ml, normal range 0-35) and benign ovarian tumors (median 119.59 IU/ml; p <0.05)."
  6. Bluebell

    Bluebell Senior Member

    A quick note about my optic nerve damage and B12.

    I finally received the Perque Activated B-12 Guard hydroxocobalamin in the post yesterday. After going without supplements for quite a number of weeks in order to have "natural" results on my blood/urine/saliva tests, I'm now ready to get started down the supplementation road to a methylation protocol!

    Even though I've read the Wikipedia entry on Vitamin B12 a number of times in the last 6 months, these 2 parts jumped out at me tonight:

    "The term B12 may be properly used to refer to cyanocobalamin, the principal B12 form used for foods and in nutritional supplements. This ordinarily creates no problem, except perhaps in rare cases of eye nerve damage, where the body is only marginally able to use this form due to high cyanide levels in the blood due to cigarette smoking; it thus requires cessation of smoking or B12 given in another form, for the optic symptoms to abate."

    I crossed out the part about smoking in the quote above because I have never smoked. Despite my not having smoked, I still think that my body could have a big problem utilizing cyanocobalamin and/or folic acid, which might have led to my sudden and unexpected vision damage.

    The next statement gives me hope that the methylation protocol with hydroxocobalamin might make a positive difference to my vision!

    "....hydroxocobalamin is... the preferred treatment for... patients... who have optic neuropathy."
  7. Valentijn

    Valentijn Senior Member

    It's a bit interesting, because the common form in the US (cyanocobalamin) can leave cyanide behind if there's a detox problem ... and the common form in the rest of the world (hydroxocobalamin) cleans up cyanide :p
  8. Bluebell

    Bluebell Senior Member

    Greenshots, I happened to be reading a different thread tonight where someone said she is homozygous for ACAT, and I recalled that you said you'd be interested to know if others have it --
    and 2 posts down, again here:
  9. Ema

    Ema Senior Member

    Midwest USA
    Keep us posted on the repeat testing!
    Valentijn likes this.
  10. Bluebell

    Bluebell Senior Member

    Thank you Ema, that is very kind for you to follow up and see how I'm doing!
  11. Bluebell

    Bluebell Senior Member

    I have received the results for my Cortisol and DHEA-S saliva test.

    Result: My cortisol was relatively normal, except it was a little bit raised at night.

    Upon awakening: 6.2 (Reference range: 3.7-9.5 ng/ml)
    Before lunch: 2.3 (Reference range: 1.2-3.0 ng/ml)
    Before dinner: 1.3 (Reference range: 0.6-1.9 ng/ml)
    Before bed: 0.9 (Reference range: 0.4-1.0 ng/ml)

    ZRT Lab's comment on my results:
    "Cortisol is within expected range throughout most of the day but rises to a slightly elevated level at night.
    A higher night cortisol suggests some form of adrenal stressor (emotional/physical-surgery, injury or disease causing inflammation/dietary-starvation/low blood glucose from dysglycemia/microbial-bacterial, fungal, or viral infections).
    Acute effects of a high cortisol are usually associated with agitation-irritability, anxiety, and sleep disturbances.
    However, when the stressor has been chronic over a prolonged period of time (months/years) this leads to conditions such as weight gain in the waist, muscle and bone loss, depression, and immune suppression.
    A chronically high night cortisol will lower melatonin production, which is important for maintaining normal biorhythms and immune function.
    If the high night cortisol is associated with symptoms characteristic of chronic high cortisol consider means to identify and eliminate the stressor.
    Because chronic stressors and associated high night cortisol can have serious long term adverse effects on health and well being, it is important to develop strategies to identify and eliminate or reduce the stressors."

    My thoughts: I was glad that my cortisol results were pretty normal. The slightly high bedtime cortisol is not a surprise, because I am a night owl and do not get sleepy until the wee hours of the morning.

    I've always been a night owl, and it's been clear to me for 30 years that it is a deeply-embedded part of my biology, not something I could significantly alter with willpower or "sleep hygiene" tips. They've now found that many factors of a person's sleep clock/circadian clock are affected by genetics. Tonight I have spent a little time looking this up in research articles and my 23andMe data, but the genetics of it is more complicated (not just some straightforward rs numbers to punch in) so I didn't get very far. In any case, I'm pretty sure that I'm in the 10% who are "extreme owls":

    "Researchers believe 10 per cent of the population are extreme owls, 10 per cent are extreme larks and the remaining 80 per cent fall in between.
    And according to experts, it's genes rather than laziness.
    Scientists have long known that early and late risers have genetic differences. A study from the University of Surrey found that extreme larks are more likely to have a long version of a gene called Period 3, while extreme owls are more likely to have a shorter version, leading to physiological differences.
    Professor Angela Clow from the University of Westminster in London found that early risers had higher levels of [morning] cortisol, the body's main stress hormone, than the alarm-clock refuseniks."

    I can certainly look into ways of reducing my nighttime cortisol a little bit. I've seen lists of supplements and behaviors that can help with that.

    However, because the bedtime cortisol is just inside the normal limits, and is probably partially due to my genetics anyway, it's not one of my top priorities now.

    ...Unless there is something about this that I don't understand, which is always possible! For instance, I saw a mention of where a doctor might do an ACTH challenge test on a person whose cortisol appeared normal, to see if the bounce-back reaction indicated a cortisol problem in the face of stressors.

    I suspect that if I get some of my methylation system going, and if I get my DHEA level up, other physical markers like cortisol and the thyroid numbers will move closer to normal. ??

    Result: As with my blood test for DHEA-S a month ago, the DHEA-S saliva result was abnormally low.

    DHEA-S: 1.4 LOW
    Reference range dependent on age:
    Normal range for a woman of my age is between 3.5-10.
    Normal range for women aged 87 is between 2-4, so my level is below even the most elderly woman's "normal" level.

    ZRT Lab's comment on my result:
    "Chronic low DHEAS may suggest adrenal fatigue, particularly if cortisol is also low and symptoms are indicative of low adrenal function.
    DHEAS is highest during the late teens to early twenties (10-20 ng/ml) and drops steadily with age to the lower end of range by age 70-80 (2-9 ng/ml).
    Mid-life DHEAS levels in both males and females are usually in the range of 5-8 ng/ml.
    Low DHEAS may contribute to low androgen symptoms (decreased libido, depression, fatigue, memory lapses, and/or bone loss), since DHEAS is a testosterone precursor.
    In individuals with very low DHEAS (< 2 ng/ml), DHEA supplementation in the 5-25 mg dosing range usually raises DHEAS to levels seen in mid-life."

    My thoughts: It was a relief to learn that my DHEA-S is less than what an 85-year-old woman is supposed to have, because that lends objective legitimacy to how worn-out I have been feeling these last few years.

    I've looked into low DHEA-S tonight. Not having an adequate amount is hard on the body in many ways -- it harms the brain, the bones, the reproductive system, the skin, everything. They say it is often correlated with having cancer, and it is a key predictor of breast cancer, apparently:

    "...most, if not all, cancer patients present with low DHEA levels. Often a 40-year-old individual may present with DHEA quantities of an 80-to-90 year old patient."

    "Most cancer patients and those who are developing cancer have low DHEA blood levels."

    "A host of studies suggest that the lower a person's level of DHEA, the greater his risk of death....
    Low DHEA predicts breast cancer more accurately than any other known marker. Women with breast cancer consistently have lower-than-normal DHEA readings.
    Research has pinpointed low DHEA levels as a marker for many degenerative diseases and accelerated aging.
    The hormone has been implicated as a contributing factor in a host of health problems, including Alzheimer's disease, autoimmune disease and other immunological disorders, cancer, chronic fatigue syndrome, diabetes, heart disease, high cholesterol, memory problems, obesity, osteoporosis, and stress disorders."

    As I did for the CA-125 test, I've collected various views on DHEA-S levels and supplementation from some generally reputable sources (in an 8-page Word document!) The experts don't all agree. Some urge great caution regarding DHEA supplementation.

    This is my current impression:

    1. I probably do not have a serious adrenals-specific illness (going by information such as the article here insufficiency.pdf, the article here, and the article and chart here:
    My cortisol is mostly normal (and my sodium and potassium levels on my blood tests last month were normal), and I don't have a symptom profile that fits any of those conditions well.

    2. My DHEA-S is low enough that careful supplementation of DHEA might be a good idea. Low levels of DHEA-S are linked to the development of many health problems, to accelerated aging, and to fatigue and low functioning.
    Many experts/doctors say that DHEA should not be supplemented without the help of a doctor.
    It appears that a conservative approach for a female patient is to supplement daily with 5 to 10 mg of micronized DHEA by a reputable manufacturer, and to test after 3-6 weeks, then again after 3 months, to see what her DHEA-S levels are.

    3. Before a female patient supplements with DHEA, it's generally a good idea to get a picture of her reproductive hormone levels, so they can be monitored after the DHEA treatment has started. DHEA can encourage extra production of sex hormones in the body, and that might cause unwelcome symptoms, or even be harmful to the health.

    4. There are many warnings that, theoretically, DHEA supplementation could encourage hormone-related health problems such as cancers of the reproductive system/breasts. There does not seem to be much actual research evidence that this has occurred, but experts of all stripes make sure to warn patients who have hormone-related cancer, or a family history of it, not to supplement with DHEA without being under a doctor's care.
    Because of my high CA-125 test result from last month, I do not know if I have a hormone-related cancer/tumor or not, but it's quite possible that I do.

    What I've decided so far:

    -My low DHEA-S result and the possibility of DHEA replacement will definitely be something I will ask the doctor about, when I do see a doctor.

    -I have decided not to try taking any DHEA on my own, at least until after my next CA-125 test. After I get the results from that, I will decide what to do next regarding my healthcare on several fronts, including the DHEA situation.

    -If I decided later to take DHEA, I would start with 5 mg per day, and never go higher than 10 mg (unless I were urged to do so by a sensible doctor).

    -I didn't get any reproductive hormone tests done last month, but it might be wise to get a panel done now (at the same blood draw as my CA-125 repeat test), if it's not too expensive. (One of the reasons I didn't test them last month was that I read that when a woman is still menstruating, several of her hormones fluctuate so much that there is no point in testing them. Is that true?)

    -If I started to take DHEA, I would re-test DHEA-S and my reproductive hormones after 4-6 weeks, and again after 3 months, to make sure the numbers were okay.


    a. Do you have any thoughts about these Cortisol and DHEA-S test results? What might they indicate? Could this result be serious, in and of itself?

    b. Anyone have personal experience with DHEA replenishment via a supplement?

    c. Since I am still having periods, is there any point of doing reproductive hormone testing - would it be accurate?

    d. If I should do a reproductive hormones test, which would be the best one to take, and is there an affordable version? (Blood, urine, saliva?)

    e. Would a general GP/gynecologist be able to help me with this abnormally-low DHEA-S situation, or would I need to see an endocrinologist about it?

    Thank you so much for reading this! :)
  12. Ema

    Ema Senior Member

    Midwest USA
    I agree with what you wrote and your assessment. Morning is a tad low and evening is too high. I don't think it's a serious adrenal problem but the beginnings of a dysregulated pattern. I think you are on the right track with considering a supplement to lower the nighttime level.

    Do you like being a night owl or are you open to trying to shift your circadian rhythm?

    DHEA can also help normalize cortisol levels so I think taking 10 mg at night would be very helpful. It might be enough to lower your nighttime cortisol all by itself. If not, you could try an herbal formula or something like phosphatidyl serine.

    Yes, I've taken DHEA for about 2 years now. The supplements work great. I have the best luck with the micronized or lipid matrix forms. I use Pure Encapsulations right now. I take 10 mg at night now though have taken 25 mgs in the past. I aim to keep my level around 200 so I take more or less depending on my most recent labwork.

    Some people also seem to like the transdermal creams. There is one on Amazon called Twist that has been well received.

    I think you could start at 10 mg.

    Yes, absolutely.

    If cycling, it should be done on day 21 or approx 7 days after ovulation. This is a time in the cycle when levels are reasonably high and stable so the results can be compared across cycles if repeat testing is needed.

    I personally prefer serum tests (privatemdlabs has a well priced package if paying for it out of pocket). Saliva tests are only good in my opinion only before being on any sort of hormone supplementation. Which is fine but doesn't give you a baseline then if you then embark on BHRT if the saliva results are low.

    I don't see any point in doing any testing though if you are sure that you won't want to supplement if the levels are low due to valid concerns about hormone sensitive cancers. Before I test, I always try to ask myself if what I am doing will change depending on the result of this test. If the answer is no, I save my money. Otherwise, I end up getting results that suggest one thing and feeling doubly conflicted.

    Probably most traditional minded doctors will dismiss DHEA regardless of the wealth of studies showing that it is helpful. I don't think endocrinologists would be any help. An open-minded GP would probably be your best shot. If they are prescribing bioidentical hormone replacement (and not all do), they might be able to talk to you about DHEA. But most will probably just tell you not to take it just in case to cover their you-know-whats and won't bother to mull over whether it would be beneficial for you or not.

    I obviously can't tell you what to do or not to do, but I think I would lean towards taking it if I was in your position.

    Dr Sahelian describes some studies discussing DHEA and cancer here:

    DHEA and cancer
    In DHEA: A Practical Guide, Dr. Ray Sahelian describes several ways in which DHEA could prevent and fight cancer. In one study, nine healthy elderly men took 50 mg of DHEA for 20 weeks. Scientists found that DHEA increased the activity of lymphocytes, which are natural killer cells that find and destroy not only viruses, but also abnormal cells that may turn cancerous. Although the number of T lymphocytes was unaffected, T cell function was increased. In this way DHEA increased the quality of the body's natural defense against cancer, not necessarily the quantity of cells that do the fighting.
    Sahelian chronicles another study that was conducted on mice and rats. In this experiment, DHEA was shown to inhibit the development of experimental tumors of the liver, breast, lung, colon, skin lymphatic tissue and other bodily tissues. Among pregnant rats implanted with a cancer-causing agent, 96 percent of the controls developed mammary (breast) tumors. Mice that were supplemented with DHEA but that otherwise received the same cancer-causing treatment had only a 35 percent incidence of mammary tumors. Dr. Inano, a Japanese researcher, concluded, "These findings suggest that DHEA has a potent preventive activity against the promotion/progression phase of radiation-induced mammary tumorigenesis."
    Correlations have also been found between decreased DHEA levels and T cell leukemia. While DHEA has already been proven to be effective in treating hairy cell leukemia, new research also suggests that it might help T cell leukemia as well. Given the correlation between adult T cell leukemia and decreased levels of DHEA, some doctors speculate that DHEA might be beneficial. Other cancer studies show that DHEA inhibits cancer cell thymidine, a factor in cellular propagation, and disrupts the oxidizing effects of chemical carcinogens. Scientists claim that DHEA modulates the effects of chemical carcinogens on cells.
    In his self-titled supplement bible, Dr. Earl Mindell, RPh, states that DHEA also appears to increase immune function. Evidence suggests that DHEA supplementation can reverse many of the immune function problems that arise as we age. Dr. Khorram found that DHEA stimulated the production of immune cells that fight against viruses and bacteria, as well as important cells called natural killer cells, which help weed out cancerous cells before they can grow.

    Learn more:

    You could also consider 7-Keto DHEA which is a non-hormonal metabolite of DHEA that does not turn into E or T. I am not sure that it confers the same benefits though as regular DHEA and I don't believe it will raise DHEAs serum levels. I am experimenting with 7-Keto along with my regular DHEA dose and I will report back on the results of my next testing in about 6 weeks.

    helen1 likes this.
  13. Bluebell

    Bluebell Senior Member

    Thank you for your great response!

    I didn't note them down, but I think in my reading, I saw a list of 4 supplements that can reduce nighttime cortisol - vitamin C, melatonin, perhaps magnesium, and 1 or 2 others (which might have been herbs). I'll look this up in more detail.

    I'm fine with upping my C and magnesium, etc.
    I am not sure about melatonin for me - I think there is a question about taking it if one might have cancer.

    I have also seen where lecithin is meant to reduce cortisol.
    [Note: I actually tried taking lecithin for 3 days a couple of days ago, as part of dipping my toe into the water with Rich's Simplified Methylation Protocol (just to see how it would go, because I'm kind of confuzzled about the complicated and time-consuming addressing of all the mutations that is required in the other methylation protocols, and I really just want to get some real B12 and real B9 in my body as soon as possible, to see if they will help my compromised vision.) I will be writing a new post specifically about that experience with Lecithin, but it was such a negative thing that it made me worry about the rest of the methylation factors which are supposed to be more intense, if one 1200 mg capsule of simple sunflower Lecithin can batter me like that!]

    When I decided to stop the lecithin, I wondered if perhaps I should take phosphatidyl choline and/or phosphadityl serine as a standalone supplement, if it would do what Rich meant for the lecithin to do in the SMP - although maybe the isolated forms would be even more harsh on my system than the lecithin was. The lecithin kept me up for 2 hours in the middle of the night the second night I took it, and up almost the entire night the next night. And I thought it was supposed to be calming! I basically had extended hot flashes or something (which I've never had before), one lasted for 5 hours and knocked me out for the next 24 hours. ...I thought, "Oh man, is this what Greenshots warned me about? I'm having a surge, just like she said!" But I didn't think that her warning was about lecithin, though.]

    I do like being a night owl and it's the way I am fundamentally wired, but I am open to shifting my rhythm -- anything to be healthier and feel better.

    I've tried many things over the years to bring my circadian rhythm forward in the day (except for melatonin), and they haven't worked. I even wrote my high school term paper on this very subject, back in the early 1980s! That was when scientific journal articles were a bear to find and to take handwritten notes from, in dusty stacks at a university library in my town. :) Thank goodness for Pubmed now. (What kind of weird kid writes a high school research paper on this topic, and graphs her body temperature throughout the day etc.? :p )

    Does it lower cortisol right then and there when it's taken -- or for what reason do you say to take it at night?
    Sahelian: "Since DHEA can increase alertness, morning use is best; although each individual is unique and some prefer mid-day or even bedtime dosing. Bedtime dose should be very low in order not to disturb sleep."
    "Replacement consists of a single oral dose of 25-50 mg DHEA in the morning."

    Makes sense, I'll look into the prices and panels at privatemdlabs and labsdirect.

    Yes, I will have to weigh it up.

    Two sources I read said that they didn't worry about the hormone sensitive cancers because having a higher DHEA level is so helpful to the body generally, and DHEA has been shown in research to help fight active cancers that are not hormone-sensitive. One of those internet sources who said not to worry about taking it alongside a hormone sensitive cancer is quite a nutcase, so I don't really listen to what he says, but the other source seemed reasonable -- yet they are the only two who mentioned it, and all the other DHEA proponents warned against taking it if there is any potential of having a hormone-sensitive cancer.

    This is good to know.
    That really helps me to feel better about trying to navigate through whatever I can learn and act on by myself, before turning to a doctor when I have a clear idea of what I am looking for from him/her.
    [And when I have an idea of how I might be able to pay for whatever might be coming in my medical future (possibly ovarian biopsy, cancer treatment, MS brain MRIs, glaucoma eye drops at $120 per month, etc.), which will only be after either the federal government's making some kind of last-ditch effort to cover the 15 million people in those 10 states whose governors are refusing to allow the obamacare coverage for low-income adults who don't have children, or my having to move to another state on my own. I might not know the answer to that for 5 months (end of December), and then I'd have to wait the 3 more months that the legislation requires before beginning treatment for pre-existing conditions. But these months will go fast. The last few have flown by!]

    Yes, I had seen that mentioned as an option for people with hormonal cancers or homonal imbalances, but I agree that it did not seem to have many of the benefits of straight DHEA.

    Looking forward to your update on how the 7-Keto DHEA went for you.

    I was interested to see his current thoughts on DHEA on his website - he might have become more conservative about it than he was when he wrote his book.

    Excerpts from his site - I changed the order of his sentences around when I put them in my Word document of research, but they are all from his DHEA page:
    "A DHEA supplement may benefit those who have adrenal deficiency and low levels. The benefits from a supplement (in men and women who are deficient) include improved sense of wellbeing, more alertness and stamina, and enhanced sexual interest and libido.
    In those cases where hormone level testing has been done due to suspicion of potential endocrine problems, if the DHEA level is very low, then it may mean that the patient would benefit taking 5 to 10 mg.
    It is extremely unlikely that 5 mg a day causes liver damage.
    DHEA supplements are not likely to stop the body's own production.
    The dosage needs to be individualized to each person's needs. This is based on regular evaluations of a basic physical exam, including blood pressure, heart rate, examination of hair and skin, evaluation of routine blood studies, and monitoring of mood, sleep patterns, energy levels, and motivation. Women need to have regular breast exams and Pap tests. Men need to have their prostate exam. Although blood or saliva DHEA levels are important to monitor, in the end, the important point to keep in mind is what kind of influence DHEA or other hormones are having on our brain, organs and tissues. It's possible that taking too much of these hormones could actually shorten lifespan. DHEA and pregnenolone are not like vitamin C. More is not necessarily better. There's a smaller range to play with. I get uncomfortable when I hear of doctors prescribing 25 or 50 mg a day to their patients.
    Since DHEA can increase alertness, morning use is best; although each individual is unique and some prefer mid-day or even bedtime dosing. Bedtime dose should be very low in order not to disturb sleep.
    It would certainly be safer if there were times when one stops taking these hormones. You could call this 'cycling' or I call it taking 'hormone holidays.' There are many ways to do this. You could take these hormones every other day, five days on, two days off, take them for a week and off a week or take them for three weeks and off a week.
    DHEA is converted in the body to androgens (such as testosterone) and estrogens, thus influencing practically every organ and tissue in the body, including the brain. However, the physiological role of this hormone has been studied for over three decades and still eludes final clarification. What we know is that DHEA is secreted by the adrenal cortex, and it exerts its action either indirectly in peripheral tissues after its conversion to androgens and estrogens, or directly as a neurosteroid through the interaction with neuronal receptors. Pregnenolone converts into DHEA and progesterone. DHEA does not convert into progesterone, rather it converts into estrogen and testosterone.
    Blood levels of all the steroid hormones that derive from DHEA metabolism are often increased when people take this hormone pill. This may lead to both beneficial and harmful effects. The overall benefit from a supplement must be balanced against potential side effects.
    I think a maximum of 5 mg is acceptable when used occasionally. Hormones are powerful substances. They can be very helpful if used appropriately but can cause harm if misused.
    I do not feel comfortable with the high dosages of DHEA, pregnenolone and 7-keto DHEA supplements sold over the counter.
    DO NOT EXCEED more than 5 mg a day on a long term basis. Blood and saliva testing are not reliable ways to determine how much DHEA you should take because blood levels do not give a clear view on how this hormone is interacting within cells in the brain, skin, hair, liver, breast, prostate, and other tissues and organs.
    If you really do need to take a DHEA supplement, use the smallest amount that works in order to prevent unpleasant reactions. Take frequent breaks which I call 'hormone holidays.'
    DO NOT TRUST ANYONE - no matter what his or her credentials - including professors at academic centers - WHO SAYS A DHEA SUPPLEMENT IS SAFE IN HIGH DOSES WHEN TAKEN FOR PROLONGED PERIODS.
    High dosing for prolonged periods - many years - could theoretically increase the risk for certain cancers such as breast cancer and prostate cancer. It is well-known that excess exposure to many types of hormones, such as androgens, progesterone and estrogens, increases the risk for certain types of cancer.
    Any androgenic steroid, such as DHEA, testosterone and androstenedione can cause the side effect of hair loss or thinning in susceptible individuals. DHEA is likely to raise levels of testosterone and dihydrotestosterone (DHT) in the hair follicles. Too much DHT will lead to hair loss.
    High dosages of pregnenolone and DHEA, generally more than 10 mg, cause heart palpitations and irregular beats in some users. In some people this can occur on dosages as low as 5 mg whereas others may take 25 mg or more to notice an arrhythmia. I believe that the highest dose of these hormones sold over the counter should be no more than 5 or 10 mg.
    A few years ago I purchased a dozen DHEA products on the market and sent them to a laboratory to be tested. They all were accurate and true to their label.
    DHEA and pregnenolone can sometimes enhance color perception and vision."
  14. Bluebell

    Bluebell Senior Member

    To Ema and/or anyone else, which female hormones should I get tested, in order to figure out if supplemental DHEA might affect them down the road?

    I've looked at the female hormone tests offered on Life Extension, Labsdirect, and PrivateMDLabs. As usual, there are several permutations offered.

    Is this one enough: $59.99
    Estradiol, Serum
    Testosterone, Serum

    Or do I need the advanced: female hormone panel#1859 $159.99
    Which subtracts:
    Which adds:
    Estrogens (Total), Serum
    Total Testosterone
    (and DHEA-but I don't need that one at the moment)
  15. Bluebell

    Bluebell Senior Member

    I just wanted to say that I discovered in my test results from last month the Free T3 test that I thought I had not ordered. This result was not in the "Thyroid Profile" section of the report, it was on another page, wedged between Homocysteine and Antinuclear Antibodies, and it was called Triiodothyronine, Free so it didn't stand out to me as being "Free T3".

    The result is: Triiodothyronine Free, Serum: 2.5 pg/mL (reference range: 2.0-4.4)

    my Reverse T3 was: 26.3 ng/dL, High (reference range: 9.2-24.1)
    my general T3 was: 91 ng/dL (reference range: 71-180)

    The Stop the Thyroid Madness website says at
    "dividing the Free T3 by the Reverse T3 (Free T3 ÷ RT3).... For healthy amounts of RT3, the ratio result should be 20 or larger."
    "If you use the total T3, you are looking for a ratio greater than 10."

    As figured by their special calculator at (which converts pg/mL and ng/dL to something that can be compared):
    My Free T3 divided by Reverse T3 = 9.5 (thus, not greater than 20)
    My T3 divided by Reverse T3 = 3.5 (thus, not greater than 10)
  16. Ema

    Ema Senior Member

    Midwest USA
    The Advanced panel is the best for me. With the coupon, it's $139.

    You also get free T.

  17. Ema

    Ema Senior Member

    Midwest USA
    You could tell you had an RT3 problem just by your over range RT3 in your case. That said, I don't believe the best way to fix it is by taking T3 only but by increasing the amount of t3/t4 preparation to compensate for the resistance.

    2.5 is pretty crap for FT3 unfortunately. But I'm not surprised it is low given your RT3 either.

  18. Bluebell

    Bluebell Senior Member

    Thank you for sharing your knowledge!

    It's good to know what I'm dealing with.
  19. Crux

    Crux Senior Member

    Hi Bluebell;
    I hope that the CA 125 test result was a fluke, but I thought I would bring up a couple of suggestions for substances that may discourage cancer, at least.

    EGCG, a green tea extract, and Curcumin from the spice turmeric, have shown anti-carcinogenic and anti-inflammatory properties.

    Another thing to consider, though the studies are inconclusive, is zinc deficiciency. It's a tough one because, in cancer, the evidence shows a dyshomeostasis...
    But, though there are many causes for elevated cortisol, zinc deficiency is one. B6 is necessary for zinc metabolism... I wonder if that is one reason for zinc dyshomeostasis.

    My personal experience with zinc supplementation has been good, except when I took too much. A couple of years ago, I had an elevated IGF-1. It could have meant many things, including cancer, but after research, I guessed that zinc deficiency was a possibility. Turns out, it was. In a years time, it reduced the IGF-1 by over 100 pts. I was lucky that time.

    I've taken EGCG and Curcumin off and on, and found them to be helpful, but I haven't done testing. They both have some stimulant properties. ( better taken earlier in the day). They both tend to slow the bowels. ( I take potassium to mitigate that.)

    EGCG and green tea may also lower folate absorption.

    Best to you!
  20. Sea

    Sea Senior Member

    NSW Australia
    I have no input for you Bluebell but I'm following your thread and waiting in suspense for your repeat CA125 test result. I hope you find some answers that will help you soon

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