here - Rocky Mountain Analytical
Transcription
here - Rocky Mountain Analytical
Accession # 00213132 Cassy Price PO Box 412 Cochrane, AB T4C 1A6 DOB: 1990/03/01 Gender: Female Provider: Dr. Gillson Ordering physician: 105 - 32 Royal Vista Dr NW Accession # 444444 Jane Doe Collection Times: 2015-08-11 2015-08-11 2015-08-11 2015-08-11 05:53PM 07:36AM 09:38AM 09:53PM P re op a u s al Sex Hormones R ge low limit en an m Hormone Testing Summary your result high limit P ostmenopausal range 27.0 62.0 15.8 6.0 6.0-17.0 How to read the graphical representation of results 5.5 1.9 17.8 20.0 0.3-2.0 Total Estrogen 17.3 Progesterone Testosterone (Serum Equivalent, ng/mL) (S um of 8 Es trogen Metabolites ) See Pages 2 & 3 for a thorough breakdown of sex hormone metabolites Adrenal Hormones Total DHEA Production (ng/mg) 400 Age 20-40 40-60 >60 Daily Free Cortisol Pattern Cortisol 320 240 400.0 Range 800-2500 530-1550 400-1350 2208.0 2500.0 Total DHEA Production (DHEAS + Etiocholanolone + Androsterone) Patient Values 160 80.0 High Range Limit 309.0 180.0 2240.0 4072.0 4300.0 80 24hr Free Cortisol Low Range Limit 0 Waking (A) Morning (B) Afternoon (C) (A+B+C+D) Night (D) cortisol metabolism Metabolized Cortisol (THF+THE) (Total Cortis ol Production) Free cortisol best reflects tissue levels. Metabolized cortisol best reflects total cortisol production. See pages 4 and 5 for a more complete breakdown. Patient Reported Hormone Therapies: ROA 1=oral, 2=sublingual, 3=transdermal cream, 4=transdermal gel, 5=vaginal/labial, 6=rectal mucosa, 7=patch, 8=pellet, 9=injection, 10=other All units are given in ng/mg creatinine P atient reports regular menstrual cycles Last Menstrual P eriod - 2015-07-21 P rogesterone Serum Equivalent is a calculated value based on urine pregnanediol. This value may not accurately reflect serum when progesterone is taken by mouth. Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 FINAL REPORT 08/26/2015 Page 1 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com Accession # 00213132 Cassy Price PO Box 412 Cochrane, AB T4C 1A6 DOB: 1990/03/01 Gender: Female Provider: Accession # 444444 Collection Times: 2015-08-11 2015-08-11 2015-08-11 2015-08-11 Category Test Progesterone Metabolism b-Pregnanediol a-Pregnanediol Androgen Metabolism DHEAS Androsterone Etiocholanolone Testosterone 5a-DHT 5a-Androstanediol 5b-Androstanediol Epi-Testosterone Estrogen Metabolites Estrone(E1) Estradiol(E2) Estriol(E3) 2-OH-E1 4-OH-E1 16-OH-E1 2-Methoxy-E1 2-OH-E2 Normal Ranges Estrone (E1) Estradiol (E2) Estriol (E3) 2-OH-E1 4-OH-E1 16-OH-E1 2-Methoxy-E1 a-Pregnanediol b-Pregnanediol Luteal 12-26 1.8-4.5 5-18 4.6-14.4 0-1.8 1-3.5 2-5.5 120-500 450-1400 05:53PM 07:36AM 09:38AM 09:53PM Result Units Normal Range Below range Below range 191.0 36.0 ng/mg ng/mg 450 - 1400 120 - 500 Within range High end of range Above range High end of range Above range Within range Above range Below range 102.0 1204.0 902.0 17.3 13.2 44.6 41.5 2.6 ng/mg ng/mg ng/mg ng/mg ng/mg ng/mg ng/mg ng/mg 23 - 350 399 - 1364 371 - 765 5.5 - 17.8 0 - 8.8 22 - 66 6 - 32 4.5 - 22.3 Below range Below range Below range Below range Within range Below range Below range Low end of range 9.7 0.6 1.7 2.0 0.3 0.5 1.5 0.16 ng/mg ng/mg ng/mg ng/mg ng/mg ng/mg ng/mg ng/mg 12 - 26 1.8 - 4.5 5 - 18 4.6 - 14.4 0 - 1.8 1 - 3.5 2 - 5.5 0 - 1.2 Postmenopausal 1.3-6.7 0.2-0.8 0.8-3.7 0.4-1.9 0-0.3 0.1-0.6 0.2-1.0 Oral Pg (100mg) 750-2300 2300-6000 5.0-34 28-135 Follicular 4.0-12.0 1.0-2.0 N/A N/A N/A N/A N/A Ovulatory 22-68 4.0-12.0 N/A N/A N/A N/A N/A 25-100 100-300 25-100 100-300 Specimen analyzed by Precision Analytical McMinnville, OR 97218 CLIA Lic. #38D2047310 Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 FINAL REPORT 08/26/2015 Page 2 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com HOW TO READ YOUR RESULTS: Hormones are presented on this page graphically in the order the body metabolizes them. Arrows represent conversion from one hormone to another. The stars represent the low and high limits of the reference ranges ( see example, right ). The number in the middle is your result. Pregnenolone Progesterone Metabolism female your result Reference Range Limit (low) Reference Range Limit (high) Androgen Metabolism Age-Dependent DHEAS Ranges 450.0 23.0 191.0 1400.0 b-Pregnanediol DHEAS DHEA m lR Pre 17.8 17.3 a us a ge 5.5 A weighted average of 36.0 op en an Progesterone 120.0 DHEAS 30-350 10-100 5-50 Age 20-40 40-60 >60 350.0 102.0 progesterone metabolites 500.0 Postmenopausal range Progesterone itself is not a-Pregnanediol Androstenedione found in urine in Testosterone measurable levels Androstenedione Estrogen Metabolism 5ß 5α 12.0 371.0 765.0 902.0 399.0 9.7 26.0 1.8 5.0 1.7 18.0 1364.0 1204.0 Estrone(E1) Etiocholanolone 4.5 0.6 Estriol(E3) Estradiol(E2) Androsterone primary estrogens (E1, E2, E3) Testosterone 5ß 5α Normal Estrogen Metabolism 1.0 5α -DHT Less Androgenic 0.5 3.5 (5ß) Low protective pathway Most potent androgen Metabolites High (5α) 16-OH-E1 2-OH 70% 4-OH 10% 16-OH 20% Patient Estrogen Metabolism 0.3 5a-Reductase Activity 0.0 1.8 4-OH-E1 5α -metabolism makes androgens more androgenic, most 2-OH 4-OH 16-OH 70.1% 10.8% 19.1% notably 5α -DHT is the most potent testosterone metabolite (~3x more potent than testosterone itself). 5α -Reductase 4-Methoxy-E1 (Protective, but not enough in urine to measure) activity is assessed using the ratio of Androsterone (5α ) to Etiocholanolone (5ß). 4-OH-E1 Low High 2.0 1.5 5.5 4.6 2.0 14.4 methylation (protective) Methylation-activity 2-Methoxy/2-OH Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 2-Methoxy-E1 2-OH-E1 FINAL REPORT 08/26/2015 If not methylated, 4-OH-E1 can bind to and damage DNA Page 3 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com Accession # 00213132 Cassy Price PO Box 412 Cochrane, AB T4C 1A6 DOB: 1990/03/01 Gender: Female Advanced Adrenal Assessment Provider: Accession # 444444 Collection Times: 2015-08-11 2015-08-11 2015-08-11 2015-08-11 Category Creatinine Test Creatinine A (Waking) Creatinine B (Morning) Creatinine C (Afternoon) Creatinine D (Night) Daily Free Cortisol and Cortisone Cortisol A (Waking) Cortisol B (Morning) Cortisol C (Afternoon) Cortisol D (Night) Cortisone A (Waking) Cortisone B (Morning) Cortisone C (Afternoon) Cortisone D (Night) 24hr Free Cortisol 24hr Free Cortisone Cortisol Metabolites and DHEAS a-Tetrahydrocortisol (a-THF) b-Tetrahydrocortisol (b-THF) b-Tetrahydrocortisone (b-THE) Metabolized Cortisol (THF+THE) DHEAS Melatonin (*measured as 6-OH-Melatonin-Sulfate) Melatonin* (Waking) Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 05:53PM 07:36AM 09:38AM 09:53PM Result Units Normal Range Within range Within range Within range Within range 0.9 0.38 0.38 2.09 mg/ml mg/ml mg/ml mg/ml 0.3 0.3 0.3 0.3 - Within range Above range Above range Above range Within range Above range Above range High end of range Above range Above range 21.3 212.8 49.4 25.0 52.8 350.0 117.5 39.6 309.0 560.0 ng/mg ng/mg ng/mg ng/mg ng/mg ng/mg ng/mg ng/mg ug ug 10 - 36 35 - 100 12 - 27 0 - 15 30 - 90 80 - 185 40 - 85 0 - 40 80 - 180 210 - 370 Low end of range Within range Above range High end of range Within range 94.0 971.0 3007.0 4072.0 102.0 ng/mg ng/mg ng/mg ng/mg ng/mg 90 - 320 750 - 1450 1300 - 2560 2240 - 4300 23 - 350 Below range 3.0 ng/mg 10 - 50 FINAL REPORT 08/26/2015 3 3 3 3 Page 4 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com CRH ST R ESS Stress (or inflammation) Hypothalamus which stimulates the adrenal glands Pituitary your result Reference Range Limit (low) causes the brain to release ACTH, Reference Range Limit (high) to make hormones Pineal Total DHEA Production ACTH 10.0 Age 20-40 40-60 >60 50.0 3.0 Range 800-2500 530-1550 400-1350 Melatonin* (Waking) 400.0 DH EA Adrenal Gland 2208.0 2500.0 Total DHEA Production A patient’s catabolic vs anabolic balance can (DHEAS + Etiocholanolone + Androsterone) be estimated by observing relative DHEA (anabolic) vs cortisol (catabolic) production Cor tis ol Cortisol Met abolism 2240.0 C 4072.0 4300.0 ng ti la cu ir Metabolized Cortisol (THF+THE) ee Fr (Total Cortisol Production) C l so ti or 400 (ng/mg) Cortisone (ng/mg) 600 Daily Free Cortisone Pattern Patient Values 360 240 Daily Free Cortisol Pattern 320 Cortisol 480 240 Patient Values 160 High Range Limit High Range Limit 80 120 Low Range Limit 0 Waking (A) Morning (B) Low Range Limit Afternoon (C) Night (D) tis o Co r 210.0 560.0 l and 370.0 0 Waking (A) e interconv ert (11bC ortis on Morning (B) HS D and are metaboliz ed to THF & THE for exc retion 80.0 309.0 180.0 24hr Free Cortisol (A+B+C+D) (A+B+C+D) More cortisone metabolites (THE) Calgary, Alberta, Canada T3R 0H9 Night (D) ) 24hr Free Cortisone Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Afternoon (C) More cortisol metabolites (THF) FINAL REPORT 08/26/2015 Page 5 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com Patient Notes NOTE: The report format has changed recently with the addition of a summary page when ordering the dutch Complete. New features include Total Estrogen (a total of all measured estrogens), Progesterone Serum Equivalent (based on excellent urine, serum correlation) and Total DHEA Production (total of DHEA metabolites). Thank you for tes ting with Precis ion Analytical, Inc. Due to the complexity of the analys is , you may need the guidance of your healthcare provider in order to properly interpret s ome of your res ults . The information here is intended to as s is t you in unders tanding your res ults in conjunction with your vis it with your provider and is not intended to diagnos e or treat any s pecific dis eas e. You may want to s kip to "Reading the Report" firs t for an explanation of how to read the report and background information on urine hormone tes ting before continuing with the report. You will find information in the comments for each s ubs ection of each tes ting profile. Comments in the report that are s pecific to you ARE IN ALL CAPS. The other information is general information that we hope you will find us eful in unders tanding your res ults . Pleas e refer ques tions to your healthcare provider. The following video link(s ) may help patients unders tand their dutch res ults . If you have only a hardcopy of the res ults , the video names can be eas ily found in our video library at www.Precis ionHormones .com. Any clinical conclus ions from res ults s hould be made exclus ively by your provider. Thes e res ults and videos are NOT intended to diagnos e or treat s pecific dis eas e s tates . The following videos may as s is t with the interpretation of your Proges terone res ults : Pos tmenopaus al Women - Proges terone-pos t-01 Premenopaus al Women - Proges terone-pre-02 The following videos may as s is t with the interpretation of your Es trogen res ults : Pos tmenopaus al Women - Es trogen-pos t-01 Premenopaus al Women - Es trogen-pre-low-02 This video may as s is t with the interpretation of your Androgen res ults : Androgens -01 YOU NOTED BEING ON BIRTH CONTROL. PROGESTERONE AND ESTROGEN LEVELS CAN BE SIGNIFICANTLY AFFECTED. TYPICALLY THOSE ON BIRTH CONTROL WILL NOT OVULATE, SO PROGESTERONE LEVELS WILL NOT BE EXPECTED TO BE WITHIN RANGE AS PROGESTERONE LEVELS DO NOT INCREASE SIGNIFICANTLY WITHOUT OVULATION. IF BIRTH CONTROL INCLUDES SYNTHETIC ESTROGEN (ETHINYL-ESTRADIOL) YOUR ESTROGEN LEVELS WILL TYPICALLY BE SIGNIFICANTLY SUPPRESSED. Progesterone Metabolism: The primary role of proges terone is to balance the s trong effects of es trogen. Proges terone metabolites are meas ured and reflect proges terone levels well. If levels are in the lower part of the reference range compared to es trogen levels , s ymptoms of too much es trogen may occur. When ordering the DUTCH Complete, you will s ee Proges terone Serum Equivalent on the s ummary page. The urine metabolites of proges terone have been proven to correlate s trongly enough to s erum proges terone to provide this value. The correlation is the s tronges t for values within the premenopaus al luteal range. Urine metabolites can at times res ult in s omewhat higher s erum equivalent res ults in the pos tmenopaus al range. For this reas on the pos tmenopaus al Serum Equivalent range is s lightly higher than typical s erum ranges . NOTE: If proges terone is taken orally (als o with s ublingual), thes e metabolites are elevated from gut metabolis m and res ults do NOT accurately reflect s erum levels . Androgen Metabolism: This group of hormones is typically thought of as “male” hormones , but they play a key role for women as well. The ovaries and adrenal glands make androgens . Tes tos terone contributes to attributes that are typically more pronounced in males than females (general and s exual aggres s ion, mus cle mas s , increas ed facial/body hair, reduction of fat depos ition, etc). Tes tos terone deficiency can lead to decreas ed s exual function, vaginal drynes s , and bone los s . 5a-Reductas e Activity: Many hormones are metabolized by the 5a or the 5b pathways . The "fan" s tyle gauge at the bottom of this s ection gives you an idea of which pathway your body favors . Why does this matter? The 5a pathway makes the very potent (3x more than tes tos terone) 5a-DHT from tes tos terone. If the your body heavily favors the 5a pathway, this may be accompanied by clinical s igns of high androgens s uch as exces s facial hair growth, s calp hair los s , acne, irritability and oily s kin. For men, too much 5a-DHT is not des irable for pros tate cancer ris k. 5b metabolites are much les s potent, and do not exert the s ame effects as 5a-DHT. Estrogen Metabolism: Es tradiol (E2) is the mos t potent es trogen and you s hould evaluate it along with es trone (E1) and es triol (E3) to check your overall es trogen s tatus . E1 and E2 are cleared from the body through three pathways . As you can s ee from the pie chart, us ually the 2-OH pathway is the main pathway and thes e "good" es trogens are protective agains t es trogen-related cancers . 16-OHE1 is s ometimes called a "bad" es trogen and 4-OHE1 is even wors e (carcinogenic). If you are making les s of the good es trogens or more of the bad ones compared to "Normal Es trogen Metabolis m," this can be improved by eating cruciferous vegetables or with certain s upplements (s uch as DIM). The las t s tep of es trogen metabolis m is methylation. The Methylation Index s hows how well the body is achieving this important s tep where 2-Methoxy-E1 is made. Methylation helps protect the body agains t the harmful effects of 4-OH es trogens . YOUR ESTROGENS ARE METABOLIZ ED MOSTLY DOWN THE 2-OH PATHWAY, WHICH IS PREFERRED. THESE METABOLITES ARE Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 FINAL REPORT 08/26/2015 Page 6 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com CONSIDERED MORE PROTECTIVE THAN THE 4-OH AND 16-OH METABOLITES. ADVANCED ADRENAL ASSESSMENT: When you are under s tres s (phys ical or ps ychological), your HPA-axis (brain talking to adrenal glands ) is prompted to produce ACTH which s timulates the adrenal gland to make the s tres s hormone cortis ol and to a les s er extent DHEA-S. Mos t cortis ol is then metabolized to "metabolized cortis ol" and levels of both "free" and "metabolized" cortis ol s hould be taken into account to correctly as s es s adrenal function. The Daily Free Cortisol Pattern: In healthy adrenal function, cortis ol levels are expected to ris e in the early morning and fall throughout the day, reaching the lowes t point right after going to s leep. Cortis one is the inactive form of cortis ol. Its pattern is of s econdary importance, but at times can give additional clarity to your provider. The daily total of free cortis ol is approximated by adding up the four individual meas urements of free cortis ol. This repres ents circulating cortis ol. Metabolized cortis ol is actually a better marker when looking at total cortis ol production. OVERALL FREE CORTISOL LEVELS ARE ELEVATED, BUT METABOLIZ ED CORTISOL (THE BEST MARKER FOR OVERALL CORTISOL PRODUCTION) IS WITHIN RANGE. CORTISOL CLEARANCE MAY BE A BIT SLUGGISH, WHICH KEEPS FREE CORTISOL LEVELS ELEVATED IN SPITE OF NORMAL OVERALL PRODUCTION. IN THIS CASE ADRENAL ACTIVITY MAY NOT BE AS OVERACTIVE AS IMPLIED BY FREE CORTISOL LEVELS. The Cortisol-Cortisone Balance: Cortis ol, which is the active hormone, can convert into cortis one, the inactive form. They convert back and forth in different parts of the body. We tell which one you make more of by looking at whether cortis ol metabolites (aTHF, bTHF) or corits one metabolites (bTHE) are made more (compared to what is normal). Balance between the two is us ually preferred, but making more cortis ol than cortis one is s ometimes good to help give you enough cortis ol if your levels are low. In s ome cas es this index is important for overall unders tanding of why s ymptoms of high or low cortis ol may be predominating. In other cas es this index is not critically important. THE RATIO BETWEEN YOUR THF/THE SHOWS A VERY STRONG PREFERENCE FOR CORTISONE. IN SPITE OF THIS, YOU DO NOT HAVE LOW CORTISOL LEVELS THEREFORE YOU MAY HAVE CHRONICALLY HIGH CORTISOL LEVELS AND THE ENZ YME THAT CONVERTS CORTISOL INTO CORTISONE IS INCREASED BRINGING YOUR CORTISOL LEVELS DOWN INTO NORMAL RANGE. YOUR ADRENAL GLANDS MAY EVENTUALLY HAVE TROUBLE KEEPING UP WITH THE DEMAND. Reading the Report: The firs t page of the lab report is a clas s ic lab report s howing each res ult and the res pective range of each hormone. Reference ranges s hown are thos e of young healthy females collecting on days 19-21 (mid-luteal phas e) of the mens trual cycle. The graphical repres entation of res ults on the page that follows allows the viewing of hormone res ults within the biochemical flowchart to more eas ily s ee the relative level of each hormone. The gauge format s hows your res ult (repres ented by the “needle” of the gauge) and the area between the s tars repres ents the reference range. The “fan” s tyle gauges are us ed for indexes /ratios . Thes e us ually tell you how "turned up" a particular metabolic proces s is . Becaus e thes e values are all bas ed on ratios there are no values or units , but they give a general idea of a particular relations hip. The middle of the gauge repres ents an average value, while the lines towards the edge repres ent res ults lower or higher than what is us ually expected. UPDATE: The DUTCH Complete report now also has a summary page for a quick overview of the most vital information. This includes a screenshot of the reported therapies. General Overview: Hormones are known as “chemical mes s engers .” They are formed in one part of the body, s ent throughout the res t, and do their work anywhere their res pective receptor is pres ent. In men, for example, tes tos terone is produced primarily in the tes tes and then s ent throughout the body. The s kin in certain areas has a lot of receptors for tes tos terone (androgen receptors ) that interact with the hormone to generate the hormonal effect of increas ing facial and body hair, for example. Typically parent hormones s uch as es tradiol (primary es trogen), proges terone, DHEA, and cortis ol (s tres s hormone) are made by organs des igned s pecifically for their production. Thes e hormones are then s ent throughout the body to exert their influence and are als o metabolized. Thes e metabolites can als o exert s ignificant influence. Es tradiol, as an example, can be turned into 2-OH and 4-OH es tradiol. One of thes e is protective and one is carcinogenic, s o meas uring parent hormones and their metabolites is very important when evaluating a pers on’s overall hormonal picture. There are many different types of hormones , but all of thos e meas ured in this tes t are cons idered “s teroid hormones .” Choles terol is the backbone to all s teroid hormones , and it s its at the top of the hormone cas cade. The adrenal glands , as an example, take in choles terol make the hormone pregnenolone, which is then converted in the adrenal into both cortis ol and DHEA-S. Es tradiol (the primary es trogen) and proges terone are s lightly more complicated but als o s tart with choles terol when made by the ovaries of cycling women. Each of thes e hormones can als o be produced in other places in the body from the hormone preceding it in the cas cade. Es trogens can be made to s ome extent from DHEA, for example, but at much lower rates as compared to ovarian production (for premenopaus al women). Before hormones can be found in the urine, they mus t be water-s oluble (s ince urine is mos tly water) or they won’t be excreted in large amounts . Mos t of the s teroid hormones are not water-s oluble. The liver or kidney mus t firs t attach another molecule (in mos t cas es s imilar to a s ugar molecule) to a hormone through a proces s known as ‘conjugation’ in order for it to be properly excreted in the urine. This proces s of making the hormones more eas ily excreted is called phas e II detoxification. As an example, conjugated Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 FINAL REPORT 08/26/2015 Page 7 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com tes tos terone that has gone through phas e II detoxification is found in the urine 100 times more than actual free (nonconjugated) tes tos terone. In the lab, we convert thes e conjugated hormones back into their original form (tes tos terone, in this cas e) and then meas ure them. For the mos t part, thes e meas urements reflect the bioavailable (or active) amount of hormone in the body. Cortis ol and cortis one are much more water s oluble and therefore are better meas ured as ‘free’ hormones (conjugates are ignored). A s ignificant amount of s cientific res earch has been done over the years to validate the us efulnes s of meas uring ‘free’ cortis ol and cortis one as well as the conjugated forms of the other hormones in urine. Epi-tes tos terone is cons idered "for res earch only" as there is no appropriate proficiency tes ting for this compound currently. Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 FINAL REPORT 08/26/2015 Page 8 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com Provider Notes NOTE: The report format has changed recently with the addition of a summary page when ordering the dutch Complete. New features include Total Estrogen (a total of all measured estrogens), Progesterone Serum Equivalent (based on excellent urine, serum correlation) and Total DHEA Production (total of DHEA metabolites). If this is your firs t report, you are encouraged to s kip to the las t two paragraphs firs t for an explanation of how to read the report and background information on urine hormone tes ting. The patient comments may s erve as introductory level. Provider comments dis cus s more complex as pects of the tes t. Comments in the report that are s pecific to your patient ARE IN ALL CAPS. The other information is general information that we hope you will find us eful in unders tanding your patient's res ults . Reference ranges updated 7/23/2015. The following video link(s ) may help providers new to dutch tes ting to unders tand the res ults . If you have only a hardcopy of the res ults , the video names can be eas ily found in our video library at www.Precis ionHormones .com. Thes e res ults and videos are NOT intended to diagnos e or treat s pecific dis eas e s tates . The following videos may as s is t with the interpretation of your Proges terone res ults : Pos tmenopaus al Women - Proges terone-pos t-01 Premenopaus al Women - Proges terone-pre-02 The following videos may as s is t with the interpretation of your Es trogen res ults : Pos tmenopaus al Women - Es trogen-pos t-01 Premenopaus al Women - Es trogen-pre-low-02 This video may as s is t with the interpretation of your Androgen res ults : Androgens -01 YOUR PATIENT NOTED BEING ON BIRTH CONTROL. PROGESTERONE AND ESTROGEN LEVELS CAN BE SIGNIFICANTLY AFFECTED. TYPICALLY THOSE ON BIRTH CONTROL WILL NOT OVULATE, SO PROGESTERONE LEVELS WILL NOT BE EXPECTED TO BE WITHIN THE LUTEAL, PREMENOPAUSAL RANGE AS PROGESTERONE LEVELS DO NOT INCREASE SIGNIFICANTLY WITHOUT OVULATION. IF BIRTH CONTROL INCLUDES SYNTHETIC ESTROGEN (ETHINYL-ESTRADIOL) THE PATIENT'S ENDOGENOUS ESTROGEN LEVELS WILL TYPICALLY BE SIGNIFICANTLY SUPPRESSED. ESTROGEN AND PROGESTERONE LEVELS MAY BE OF MARGINAL VALUE WITH SOME BIRTH CONTROL SCENARIOS. Progesterone Metabolism: Very little proges terone is found in urine, s o b-Pregnanediol is typically us ed a s urrogate marker becaus e it is the mos t abundant metabolite, but we als o tes t the corres ponding a-pregnanediol. The average of the two metabolites is reported for proges terone. When the relative levels of es trogen are higher than thos e for proges terone s ymptoms of es trogen dominance may occur. When ordering the DUTCH Complete, you will s ee Proges terone Serum Equivalent on the s ummary page. The urine metabolites of proges terone have been proven to correlate s trongly enough to s erum proges terone to provide this value. The correlation is the s tronges t for values within the premenopaus al luteal range. Urine metabolites can at times res ult in s omewhat higher s erum equivalent res ults in the pos tmenopaus al range. For this reas on the pos tmenopaus al Serum Equivalent range is s lightly higher than typical s erum ranges . NOTE: If proges terone is taken orally (als o with s ublingual), thes e metabolites are elevated from gut metabolis m and res ults do NOT accurately reflect s erum levels . Androgen Metabolism: Tes tos terone is made in the ovaries as well as the adrenal glands . In pos tmenopaus al women adrenal production is the primary s ource of tes tos terone. a-DHT (a-dihydrotes tos terone) is the mos t potent androgen (3X more than tes tos terone), but it is primarily made within the liver and target cells (it is a paracrine hormone) and not by the gonads . a-DHT is s ubs equently deactivated to a-andros tanediol within target tis s ues and then excreted. As s uch, aandros tanediol may bes t repres ents a-DHT even though its metabolic precurs or is more biologically active and well known. Only a fraction of a-DHT formed actually enters circulation as a-DHT (Tos cano, 1987). The corres ponding beta metabolites (for example b-DHT) are not androgenic. 5a-Reductas e Activity: The competing enzymes 5a and 5b-reductas e act on the androgens andros tenedione (creating andros terone and etiocholanolone) and tes tos terone (creating a-DHT and b-DHT). They als o metabolize proges terone, and cortis ol (a/b-THF). The alpha metabolites of andros tenedione and tes tos terone are far more androgenic than their beta counterparts . Cons equently, increas ed 5a-reductas e activity may be accompanied by clinical s igns of androgenicity (exces s facial hair growth, s calp hair los s , acne, irritability, oily s kin). If the patient heavily favors the 5a pathway and there are concerns of exces s androgenicity (or pros tate cancer ris k), this may be worth addres s ing. Estrogen Metabolism: There are two primary is s ues with res pect to es trogens . 1) Es trogen production (is the patient deficient, s ufficient, or in exces s ?) and 2) Es trogen metabolis m (is the metabolis m of es trogen favorable or unfavorable with res pect to hydroxylation and methylation pathways ?) While es tradiol (E2) is the mos t potent es trogen, levels of es trone (E1) and es triol (E3) s hould als o be cons idered when evaluating the patient's es trogen production. You want to compare the patient's dis tribution of metabolites from the pie chart to "Normal Es trogen Metabolis m." If they are making cons iderably les s of the protective 2-OH es trogens , you may want to cons ider s omething to up-regulate this metabolis m (DIM, I-3-C, etc). Be advis ed increas ing 2-OH metabolis m will likely lower E1 and E2. It is our pos ition that the ratio of 2:16 OHE1 is not as relevant as has been thought his torically (Obi, 2011). Providers may s till wis h to us e this index and it can be calculated by s imply dividing the two numbers . A female reference Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 FINAL REPORT 08/26/2015 Page 9 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com range for the ratio with our methodology is 2.4-6.0. The methylation index will s how you how effectively the patient is turning 2 and 4-OH es trogens into methoxy es trogens . Methylation protects agains t potentially harmful 4-OH es trogens . Supporting the methylation pathway s hould be cons idered if this index is low. PHASE I METABOLISM LOOKS GOOD FOR THIS PATIENT WITH A PREFERENCE FOR 2-OH METABOLISM. PRODUCTS TO INCREASE 2-OH METABOLISM WOULD ONLY BE CONSIDERED IF E1 AND E2 ARE HIGH RELATIVE TO 2-OH ESTROGENS AS AN OVERALL EFFORT TO LOWER ESTROGENS. ADVANCED ADRENAL ASSESSMENT: The HPA-Axis refers to the communication and interaction between the hypothalamus (H) and pituitary (P) in the brain down to the adrenal glands (A) that s it on top of your kidneys . When a phys ical or ps ychological s tres s or occurs , the hypothalamus tells the pituitary to make the ACTH, a hormone. ACTH s timulates the adrenal glands to make cortis ol and to a les s er extent DHEA and DHEA-S. Normally, the HPA-axis production follows a daily pattern in which cortis ol ris es rather rapidly in the firs t 10-30 minutes after waking in order to help with energy, then gradually decreas es throughout the day s o that it is low at night for s leep. The cycle s tarts over the next morning. Abnormally high activity occurs in Cus hing’s Dis eas e where the HPA-axis is hyper-s timulated caus ing cortis ol to be elevated all day. The oppos ite is known as Addis on’s Dis eas e, where cortis ol is abnormally low becaus e it is not made appropriately in res pons e to ACTH’s s timulation. Thes e two conditions are s omewhat rare. Examples of more common conditions related to les s s everely abnormal cortis ol levels include fatigue, depres s ion, ins omnia, fibromyalgia, anxiety, inflammation and more. Only a fraction of cortis ol is "free" and bioactive. This fraction of cortis ol is very important, but levels of metabolized cortis ol bes t repres ents overall production of cortis ol. Diurnal Free Cortisol Pattern: The primary reas on for the timing of urine collections for this tes t is to as s es s the diurnal pattern of cortis ol (and to a les s er extent cortis one). Typical urine tes ting (24-hour collection) averages the daily production of cortis ol. This approach is not able to properly characterize individuals whos e cortis ol patterns do not fit the expected pattern. Dys functional diurnal patters have been as s ociated with health-related problems s uch as fatigue. While the diurnal pattern of cortis ol is of primary interes t, the cortis one pattern may provide additional clarity in certain s ituations . Cortis ol levels us ually are at their lowes t around 1am and peak in the firs t 30-60 minutes following waking. The waking s ample repres ents the total of free cortis ol throughout the s leeping period. The daily total of free cortis ol is approximated by s umming the four meas urements . This calculated value correlates to a 24hour free cortis ol value. It is helpful to compare the relative level of 24-hr free cortis ol with metabolized cortis ol to unders tand HPA-axis activity. The total of free cortis ol for the day only repres ents about 1-3% of the total production. The total of the metabolites is a better marker for overall cortis ol production. OVERALL FREE CORTISOL LEVELS ARE ELEVATED, BUT METABOLIZ ED CORTISOL (THE BEST MARKER FOR OVERALL CORTISOL PRODUCTION) IS WITHIN RANGE. CORTISOL CLEARANCE MAY BE A BIT SLUGGISH, WHICH KEEPS FREE CORTISOL LEVELS ELEVATED IN SPITE OF NORMAL OVERALL PRODUCTION. THE HPA-AXIS IN THIS CASE MAY NOT BE AS OVERACTIVE AS IMPLIED BY FREE CORTISOL LEVELS. Cortisol-Cortisone Balance: The back-and-forth convers ion of cortis ol and its inactive form, cortis one is not a tug-of-war going on between the two 11b-HSD enzyme types within a particular tis s ue. Thes e two actions (activation to cortis ol and deactivation to cortis one) happen in different compartments within the body. The deactivation of cortis ol to cortis one (11bHSD II) occurs predominantly in the kidneys , colon, and s aliva glands . The local formation of cortis one from cortis ol in the kidney is s trongly reflected in urine. This makes the ratio of free cortis one and cortis ol a good index of this local renal deactivation (11b-HSD II) but the free cortis ol-cortis one ratio does not s peak to the overall predominance of cortis ol or cortis one. Activation of cortis one to cortis ol takes place primarily in the liver, adipos e tis s ue, gonads , brain, and mus cle. Within thes e s ame tis s ues (mos tly the liver) the free hormones are als o converted to their metabolites (cortis ol to a/b-THF, cortis one to THE), and it is the balance between thes e metabolites that bes t reflects the overall predominance of cortis ol or cortis one. The gauge at the bottom of the adrenal graphical page reflects the ratio (aTHF+bTHF)/THE. A preference for the active cortis ol is enhanced by central adipos ity, hypothyroidis m, inflammation, and s upplements s uch as licorice root extract. Cortis one formation is enhanced by growth hormone, es trogen, coffee and hyperthyroidis m. THE PATIENT'S THF/THE RATIO IMPLIES A VERY STRONG PREFERENCE FOR THE DEACTIVATION OF CORTISOL TO CORTISONE. IN SPITE OF THIS, THE PATIENT DOES NOT PRESENT WITH LOW CORTISOL, SO THIS INCREASED 11b-HSD II ACTIVITY MAY BE IN RESPONSE TO CHRONICALLY HIGH CORTISOL LEVELS. THE ADRENAL GLANDS MAY EVENTUALLY HAVE TROUBLE KEEPING UP WITH DEMAND IF ADRENAL SUPPORT IS CONSIDERED, THE INCLUSION OF LICORICE ROOT MAY BE WISE TO AVOID AS IT MAY EXACERBATE THE CORTISOL ELEVATION. Reading the Report: The firs t page of the lab report is a clas s ic lab report s howing each res ult and the res pective range of each hormone. Reference ranges s hown are thos e of young healthy individuals with females collecting on days 19-21 (midluteal phas e) of the mens trual cycle. The graphical repres entation of res ults on the page that follows allows the viewing of hormone res ults within the biochemical flowchart to more eas ily s ee the relative level of each hormone. The gauge format s hows the patient res ult (repres ented by the “needle” of the gauge) and the area between the s tars repres ents the reference range. Each gauge is plotted s o that an identical place on two gauges repres ents the s ame res ult relative to the normal range. For example, a res ult directly in the middle of the gauge repres ents an average pers on's res ult, not the mathematical average of the high and low limits of the range. This makes it eas y to s pot abnormally low or high metabolis m at different points in the hormone cas cade. Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 FINAL REPORT 08/26/2015 Page 10 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com Reference ranges are typically s et at the 20th to the 80th percentile of young, healthy individuals (DHEAS for example). This means that a res ult at the low end of a range is lower than 80 percent of young, healthy individuals . Likewis e a res ult at the high end of a range is higher than 80 percent of the population. Some reference ranges are s et more widely. For example, s lightly elevated proges terone is not generally cons idered problematic, s o its metabolites have reference ranges that extend further (90th percentile ins tead of 80th). The “fan” s tyle gauges are us ed for indexes /ratios . Becaus e thes e values are all bas ed on ratios there are no values or units , but they give a general idea of a particular relations hip. The middle of the gauge repres ents an average value, while the lines towards the edge repres ent res ults lower or higher than mos t (80%) of the population. Being outs ide of any range is not always cons idered unfavorable. For example, to methylate es trogens very effectively may have pos itive cons equences . UPDATE: The DUTCH Complete report now also has a summary page for a quick overview of the most vital information. This includes a screenshot of the reported therapies. What is actually meas ured in urine? In blood, mos t hormones are bound to binding poteins . A s mall fraction of the total hormone levels are "free" and unbound s uch that they are active hormones . Thes e free hormones are not found readily in urine except for cortis ol and cortis one (becaus e they are much more water s oluble than, for example, tes tos terone). As s uch, free cortis ol and cortis one can be meas ured in urine and it is this meas urement that nearly all urinary cortis ol res earch is bas ed upon. In the Precis ion Analytical Adrenal Profile the diurnal patterns of free cortis ol and cortis one are meas ured by LC-MS/MS. All other hormones meas ured (cortis ol metabolites , DHEA, and all s ex hormones ) are excreted in urine predominately after the addition of a glucuronide or s ulfate group (to increas e water s olubility for excretion). As an example, Tajic (Natural Sciences , 1968 publication) found that of the tes tos terone found in urine, 57-80% was tes tos terone-glucuronide, 14-42% was tes tos terone-s ulfate, and negligible amounts (<1% for mos t) was free tes tos terone. The mos t likely s ource of free s ex hormones in urine is from contamination from hormonal s upplements . To eliminate this potential, Precis ion Analytical removes free hormones from conjugates (our tes ting can be us ed even if vaginal hormones have been given). The glucuronides and s ulfates are then broken off of the parent hormones , and the meas urement is made. Thes e meas urements reflect well the bioavailable amount of hormone in mos t cas es as it is only the free, nonprotein-bound fraction in blood/tis s ue that is available for phas e II metabolis m (glucuronidation and s ulfation) and s ubs equent urine excretion. Dis claimer: the filter paper us ed for s ample collection is des igned for blood collection, s o it is technically cons idered "res earch only" for urine collection. Its proper us e for urine collection has been thoroughly validated. Precision Analytical Rocky Mountain Analytical 3138 Rivergate Street #301C 105 - 32 Royal Vista Drive NW McMinnville, OR 97218 Calgary, Alberta, Canada T3R 0H9 FINAL REPORT 08/26/2015 Page 11 of 11 CLIA Lic. #38D2047310 UrineHormones.com www.rmalab.com