Hormone Testing
Measuring hormone levels is essential for the proper diagnoses of perimenopause, menopause, andropause or other disease states such as hypothyroidism and adrenal exhaustion (chronic fatigue syndrome), which all exhibit similar and overlapping symptoms making an accurate diagnosis based on symptoms alone very difficult. Hormone level testing also enables you to closely monitor your hormones ensuring they all remain adequately balanced and within the optimal physiological range.
The hormone test results used in conjunction with any symptoms you have are invaluable tools when designing an Individual Bioidentical Hormone Replacement Therapy (IBHRT) regime. It is very surprising, not to mention dangerous, how many women and men on HRT have never had their hormone levels tested. Hormonal imbalances that are not accurately identified and appropriately treated may lead to inappropriate treatments with very serious side effects so the importance of monitoring their levels cannot be overstated. There is currently some criticism against hormone testing by some medical practitioners whom claim they are worthless and that it is best to diagnose and dose hormones based on symptoms alone. We do not agree with this argument as many conditions share similar symptoms making it difficult to differentiate between them making an accurate diagnosis difficult. In addition some people can tolerate very high hormone levels or hormone imbalances and display no symptoms yet these imbalances in the long term could potentially create a problem such as cysts, fibroids or cancer. The critics of hormone testing usually pay little to no attention to the appropriate balance of hormones which can only be accurately determined by hormone testing. A couple of common examples we see regularly are given to illustrate the necessity for testing. Firstly if a women presents with hot flushes many practitioners will assume she is menopausal and requires estrogen when in actual fact the hot flushes were caused by high cortisol levels. By giving estrogen to her is an inappropriate and possibly dangerous treatment which may cause further hormone imbalances and side effects. Secondly, again a women presents with hot flushes which were caused by excessively high levels of estrogen which resulted in a down regulation of her estrogen receptors causing her hot flushes. By assuming it is caused by an estrogen deficiency and giving estrogen to this women, which would be the most common diagnosis based on her symptoms, would make her condition worse. Finally in order to reduce the long term risks of hormone replacement an appropriate balance of the three estrogens is essential and also their balance with progesterone. Therefore ongoing monitoring is essential in order to ensure a healthy hormone balance is maintained throughout therapy. These can only be determined by hormone testing. Here are only a couple of examples we see in our practice which emphasise the need for hormone testing.
As a generalisation I recommend women test for estriol, estradiol, estrone, progesterone, testosterone, DHEA, cortisol and thyroid (T3,T4 and reverse T3) hormones. The first five hormones make up the basis of IBHRT while measuring DHEA, cortisol and thyroid hormones may indicate if adrenal exhaustion or hypothyroidism are present, which have been implicated in perimenopause, menopause and fatigue type conditions. Men should measure estradiol, estrone, progesterone, testosterone, DHEA, DHT, cortisol and thyroid (T3,T4 and reverse T3) hormones. Ideally levels should be tested first thing in the morning before breakfast as elevated sugar levels after meals are reported to reduce testosterone levels thus giving an inaccurate result.
Important note for women: If you are still cycling then it is very important that the test is done between days 19 to 23 of your cycle (luteal phase) assuming it is a 28 day cycle. If the test is done outside this range then the results obtained are of only limited use. In addition make sure that the estrogens and progesterone are ordered and do not settle for FSH and LH tests which is what the majority of doctors will order as these values are of little value when comparing hormone balance.
Blood Tests ‘v’ Saliva Tests ‘v’ Urine Tests
(1) Blood tests are commonly used to determine hormone levels by most mainstream physicians which will measure the total amount of hormones in serum. This type of hormone testing is considered the least accurate of all methods available. These serum tests are unable to distinguish the protein-bound, and therefore inactive form of the hormone, from its free and biologically active form, thus giving only a rough estimate of your hormone levels. This may lead to inappropriate diagnosis as quite often total hormone levels are within normal limits but once the free and active levels are tested deficiencies are identified. In addition serum test results only reflect hormone levels outside the cells in the serum and do not reflect levels else where in the body where they are actually active. And finally serum tests are not widely available for estriol and estrone in Australia. Therefore two very important estrogens will go undetected when using serum analysis and quite often we see test results where estradiol is normal however estrone is elevated which is a problem that would go undetected by blood tests.
When monitoring hormone levels while on transdermal replacement therpapy serum testing is not accurate. This is because once absorbed through the skin hormones bind to red blood cell membranes in the blood in order to minimise unfavorable interactions with the aqueous water and the fat loving hormones. Once your blood sample is taken it is centrifuged and the red blood cells along with the hormones are removed prior to analysis. This phenomenon was described by Frank Z. Stanczyk (see references) for transdermal progesterone but it also seems to occur to a lesser extent for all other hormones. Serum tests show no increase in progestreone levels after weeks of applying progesterone cream whereas saliva tests show an increase only after a couple of hours! This is a significant problem monitoring levels if you are using transdermal hormone creams. To illustrate this problem further clinical trials performed by the American Academy of Anti-Aging on over 300 patients revealed that every patient whose hormone levels were deemed at optimal levels by serum blood tests had in actual fact excessive levels based on saliva tests. The doses used to achieve optimal serum levels were higher than standard physiological doses which was all that was required to achieve optimal levels by saliva tests. In every case the patients doses were reduced until saliva tests reflected optimal levels. In our own practice we see this same phenomena on a regular basis with those patients being monitored by serum blood tests – that is their current doses are too high!
The facts are there has never been a single study correlating serum values for topically administered hormones to actual tissue levels or to long term effectiveness. Most mainstream physicians have accepted serum testing as the “gold standard” without any science which is based on some false assumptions. You should never use serum testing for judging effectiveness or hormone levels from topical application - Stanzyck’s article proves this for progesterone and clinical observation sees it occuring with most other hormones as well.
NOTE: If you are using troches then blood tests or urine tests are recommended as hormone residues in the mouth can affect saliva test results for up to 36 hours after your last troche dose. It is not wise to wait 36 hours and then do the saliva test as these hormones have a short half life and will be mostly eliminated from your system so you will only be measuring baseline levels. Serum tests will detect progesterone when it is taken orally or by troche.
(2) 24 hour urine hormone testing is one of the most accurate methods of all and ideally should be used when ever available. The main problem with urine testing is the inconvenience of 24 hour urine collection and the fact it is the most expensive method. It does however eliminate the problem of timing the hormone test in relation to your last dose when monitoring bioidentical hormone therapy as you get an overall daily average of your hormone levels rather than a “snap shot” of their levels at the precise moment you do either blood or saliva tests.
(3) Saliva testing measures the free and therefore biologically active form of several of the major hormones in saliva – estriol, estradiol, estrone, progesterone, testosterone, DHEA and cortisol. Saliva tests have been proven to be an accurate reflection of hormone levels present inside cells, where the hormone action takes place, whereas blood tests measure hormones outside the cells. It is considered to be the gold standard for hormone analysis by the World Health Organisation (WHO) and even used by NASA. Despite the WHO’s recommendation to use saliva hormone testing and all the research to back up its accuracy it is often the most criticised and neglected method by medical practitioners, many whom refuse to order such tests as they are not informed of the differences and usually state there is no research to validate saliva testing. Click here for a list of peer reviewed published journals proving saliva testing to be superior to blood tests or click here for references that validate saliva testing.
Saliva hormone testing is a less painful and a more accurate way of determining your hormone status which can be performed in the comfort of your own home. The tests may be ordered by your doctor, or alternatively we can arrange them for you with a consultation if your doctor refuses to do so. Saliva hormone testing involves a test kit being sent to your home with printed instructions. Saliva samples are taken at a uniform time of the day for more meaningful comparisons and placed into provided containers at one or more specific times of the day, then sent directly to the laboratory for analysis. The results are then sent back to whom ever ordered the tests for interpretation and to determine the appropriate therapy.
Timing of Tests in Relation to your Last Dose
The best time of the day to collect a sample for any baseline hormone analysis for diagnosis is in the early morning (except for 24 hour urine analysis) before breakfast, and the best time of the month for women is between days 19 to 23 of a 28 day menstral cycle (day one is first day of mensus). This is when progesterone levels are apt to be highest (luteal phase) during the entire cycle. Men can do the test any day that is convenient but again before breakfast.
When doing subsequent follow up tests to monitor hormone levels while on any hormone replacement it is best to take the saliva sample 8 to 12 hour after the last dose if your using creams and capsules. This is very important in order to obtain meaningful results. If your using troches then a serum test should be done approximately 4 hours after your last troche dose. Be consistant so all follow up tests can be compared to each other. If the timing of the test is mixed on each occasion the test is performed then the results are not comparable!
For thyroid testing if a patient is on T4 (oroxine) therapy, it is best to test about 8 to 12 hours after the last dose of medication to get the best correlation of levels produced by the T4 replacement. With T3, the best time to test is 1.5 to 4 hours after the last dose. For thyroid extract (Armour thyroid), which is a combination of T3 and T4, you should test 4 hours after the last dose. Any sooner could produce a peak of T4 and any later could produce a drop off from the T3. All repeat tests should use the same timing as previous testing so results can be directly compared. If not then no direct accurate comparison can be made between tests.
Many doctors are critical of any form of hormone testing for women as they claim hormone levels fluctuate so testing is therefore useless. This is true, hormone levels do naturally fluctuate on a monthly cycle in menstarting women. However if that cycle is clearly understood the tests should be performed on a specific day of the cycle (luteal phase), as mentioned above, where we are well aware of the appropriate hormone levels for that time of the month and thus the results are meaningful. If periods are irregular it is more difficult to accurately assess hormone levels with just one sample. Therefore take samples on two different occasions before starting IBHRT to increase the chance that testing will reveal natural biological variations. Post menopausal women do not experience hormonal fluctuations so tests can be done on any day.
What to Test For
Your current signs and symptoms will help determine exactly what tests are appropriate to preform. Therefore the types of tests required is very individual however generally I would recommend a 24hr urine or saliva test for estriol, estradiol, estrone, progesterone, testosterone, DHEA, and cortisol. Thyroid hormones (T3, T4, Reverse T3) are determined by either blood tests or 24 hour urine excretion tests. All of these ideally should be measured before you start any IBHRT which will give you a good baseline assessment of your overall hormone status. From these initial results it can be determined which hormones need supplementation and the appropriate starting dose of each hormone.
It should be clarified that test results must be used in conjunction with signs and symptoms and not be totally relied upon 100% for a diagnosis and latter on to determine appropriate dosages. There is always a general optimal physiological level we try to achieve with tests however these levels can vary in some patients and this must be taken into account and can only be done so by also using symptoms to go by. Every day I am sent hormone test results from people wanting my advice on how to adjust their hormone doses. I cannot responsibly offer any advice without an appropriate background into their signs and symptoms to help make a final decision.
Interpreting Test Results
A major problem with hormone testing is the interpretation of test results. Practitioners with little experince in hormonal matters often observe results that lie at the low end of the so called “normal range” and determine that no hormone imbalance or deficiency exists thus determine no action is required. A major problem is that laboratory test “normal” ranges are defined and standardised according to statistical norms instead of physiological optimal levels. That is, mathematics rather than patient symptoms define “normal” hormone levels.
Instead of using “normal” laboratory ranges we prefer to use optimal ranges which as a general rule lie within the upper one third of the normal laboratory range. This general rule is only a guide as it does not take the appropriate balance between certain hormones into account which is also very important. Therefore it is important that someone with experience and knowledge on appropriate hormone balance views your test results for an accurate diagnosis. Often there is a significant improvement in symptoms when levels at the low end of the normal range are increased to the upper end of the normal range with supplementation. For a more detailed explanation refer to Limitations of Lab Test Reference Ranges blog on this website.
Once you have started IBHRT it is essential to retest your hormone levels after four to six weeks to ensure your hormone levels remain within the upper one third of the normal physiological range and also to ensure the supplemented hormones are absorbed and utilized by the body. If you use lozenges to deliver your hormones you must have blood tests as saliva test will be adversely affected if performed within 36 hours after your last dose. After your hormone levels have stabilized to suitable levels continue to retest at least annually for the rest of your life.
Further Monitoring
In addition to saliva/urine analysis we also recommend that both men and women have their 24 hour urine estriol, estradiol, estrone, 2-hydroxy-estrone, 4-hydroxy-estrone, 16-hydroxy-estrone levels checked. The goal is to assess and reduce any potential risk of disease by monitoring which estrogen metabolites are being produced, the relationship between metabolites, and how replacement affects metabolite levels. For more information on an unfavorable estrogen metabolite balance possibly causing breast and prostate cancer please refer to appropriate sections.
Annual breast screening and endometrial ultrasounds may also be important tests to have, in certain cases, to detect if any problems arise from hormone therapy.
Testing
Any of these tests discussed may be arranged during a consultation with Dr Michael Serafin. See Products and Services page for more information on consultations. Alternatively discuss them with your health care provider.
References
Frank Z. Stanczyk, PhD, Richard J. Paulson, MD, and Subir Roy, MD. Percutaneous administration of progesterone: blood levels and endometrial protection. Menopause: The Journal of The North American Menopause Society Vol. 12, No. 2, pp. 232-237
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June 17th, 2008 at 10:01 am
I think transdermal progesterone is left with a quandry which needs explanation to a level satisfactory to convince the research scientists – not necessarily doctors at this stage, I believe baby steps are acceptable initially:
1) The vast majority of research papers which validate the therapeutic benefits for progesterone do so by comparing the improved clinical symptoms to the serum levels of progesterone, not the saliva levels of progesterone.
2) Until transdermal progesterone raises the serum level of progesterone to the same levels as were achieved by the research scientists who validated the therapeutic benefits of progesterone, therefore transdermal progesterone cannot justifiably lay claim to achieve the same therapeutic benefits as are achieved by an increase in serum progesterone.
3) I see no possible logical basis by which the transdermal progesterone researchers can lay claim to the same therapeutic benefits as have been previously associated with increased levels of serum progesterone, until the transdermal progesterone is demonstrated to increase the serum levels of progesterone.
4) Therefore the transdermal progesterone researchers must lay claim to their own therapeutic benefits for humans (not mice, sorry) after they first demonstrate that an increase in salivary progesterone is linked to a therapeutic benefit, AND that a reduction of salivary progesterone is linked to a therapeutic decline. It is not sufficient to demonstrate only one of these relationships.
When the dosages and measurements of such studies are published in peer reviewed journals, AND repeated by at least two independent parties (all results on which we are going to base a therapy must be repeatable), then the corresponding transdermal progesterone dosages and salivary measurements as used by the researchers, are the ones we should observe.
I have not been able to find any peer-reviewed research papers which demonstrate the above.
I give you all the benefit of my doubt and I believe that you have all found the research papers which demonstrate these relationships. Well done. Perhaps one day I might find them too.
June 17th, 2008 at 11:00 am
Peter
The problem with relying on serum analysis for detecting transdermal progesterone is that it is a fundamentally flawed methodology and will never be able to demonstrate suitable serum levels. The reason for this is due to the fact that when progesterone is absorbed into the blood stream from the skin it binds to red blood cell membranes in order to minimize unfavorable interactions between the fat loving progesterone molecule with the aqueous (water) serum phase (remember oil and water do not mix!). When a patient goes for a serum blood test the blood sample is centrifuged before it is analyzed to remove all red blood cells, along with any progesterone attached to them. Therefore serum analysis cannot possibly accurately measure transdermal progesterone if most of it is being thrown out before being tested for. This phenomenon is not observed to such a degree with oral progesterone due to the fact that once absorbed it initially enters the liver (the reason why it has such poor bioavailability – 10 to 15%) where it is attached to the Sex Hormone Binding Globulin (SHBG). This protein then allows progesterone to remain in serum by minimizing the unfavorable interactions mentioned above and thus will show up in serum analysis. Therefore we cannot rely on serum testing to verify the validity of transdermal progesterone. Secondly, serum analysis only detects hormone levels in serum. It does not reflect hormone levels inside the cells where they are actually active. Therefore I cannot understand why so much emphasis has been placed on serum testing to the detriment of other methods. Saliva and urine tests both show that transdermal progesterone does indeed raise progesterone levels. The level achieved obviously depends on the dose and rate of absorption. I however usually adjust the dose until I obtain a reading within an optimal target range. I feel that the validity of both these methods of analysis has been well proven and thus more accurately reflect the true level of transdermally absorbed progesterone. Finally over the last 10 years or so I have been involved with 1000’s of women using transdermal progesterone. Our saliva/urine testing almost always shows improved progesterone levels not to mention the fact there is a great improvement in the patients symptoms – which is what it is all about!